Signatures of negative selection in the genetic architecture of human complex traits
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Abstract
We develop a Bayesian mixed linear model that simultaneously estimates single-nucleotide polymorphism (SNP)-based heritability, polygenicity (proportion of SNPs with nonzero effects), and the relationship between SNP effect size and minor allele frequency for complex traits in conventionally unrelated individuals using genome-wide SNP data. We apply the method to 28 complex traits in the UK Biobank data (N = 126,752) and show that on average, 6% of SNPs have nonzero effects, which in total explain 22% of phenotypic variance. We detect significant (P < 0.05/28) signatures of natural selection in the genetic architecture of 23 traits, including reproductive, cardiovascular, and anthropometric traits, as well as educational attainment. The significant estimates of the relationship between effect size and minor allele frequency in complex traits are consistent with a model of negative (or purifying) selection, as confirmed by forward simulation. We conclude that negative selection acts pervasively on the genetic variants associated with human complex traits. BayesS estimates SNP-based heritability, polygenicity, and the relationship between effect size and minor allele frequency using genome-wide SNP data. Applying BayesS to UK Biobank data identifies signatures of natural selection for 23 complex traits.
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Genomic features related to natural selection are enriched for loci associated with complex traits.
“Genomic features related to natural selection are enriched for loci associated with complex traits [1, 7–9].”
From Denisovan and Neanderthal archaic introgression differentially impacted the genetics of complex traits in modern populations (2022) · cites this paper as [7]
The Discussion reports signatures of natural selection on variants associated with complex traits, supporting a connection between selection and trait-associated loci. It does not establish that genomic features related to selection are enriched for those loci; its analysis concerns the relationship between SNP effects and allele frequency, not enrichment in genomic features. (LLM, conf=0.83)
Experimental — accuracy not yet measuredBackground selection appears to play a primary role in shaping the highly polygenic architecture of human traits and diseases.
“In particular, background selection (i.e., the selective removal of deleterious alleles across the genome) appears to play a primary role in shaping the highly polygenic architecture of human traits and diseases [1, 7–9].”
From Denisovan and Neanderthal archaic introgression differentially impacted the genetics of complex traits in modern populations (2022) · cites this paper as [7]
The Discussion (page not provided) reports signatures of natural selection in 23 of 28 complex traits and a high degree of polygenicity. The paper identifies the relevant process as negative selection, but these passages do not establish that background selection specifically plays a primary role in shaping the architecture of human traits and diseases. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe relative contributions of common and rare variants indicate that for many traits, particularly those with post-reproductive onset, purifying selection has had only limited effect.
“The relative contributions of common and rare variants indicate that, for many traits, particularly those with post-reproductive onset, purifying selection has had only limited effect45,56.”
From A brief history of human disease genetics (2020) · cites this paper as [56]
Common genetic variants generally have small effects on disease risk (OR <1.15), while rare variants typically have larger effect sizes (>2.0), are more likely deleterious, and tend to be removed by natural selection.
“Given what we know now, common variants generally have small effects on disease risk (OR <1.15), and rare variants typically have larger effect sizes (>2.0), are more likely to be deleterious, and tend to be removed by natural selection (Fu et al., 2013; Nelson et al., 2012; Zeng et al., 2018).”
From Defining the genetic, genomic, cellular, and diagnostic architectures of psychiatric disorders (2019) · cites this paper as Zeng et al., 2018
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Cites
Gelman, A., Carlin, J. B., Stern, H. S., Dunson, D. B., Vehtari, A., & Rubin, D. B. (2013) · doi:10.1201/b16018 · Cited by 27,276 · see citing works
Sudlow, C., Gallacher, J., Allen, N., Beral, V., Burton, P., Danesh, J., Downey, P., Elliott, P., Green, J., Landray, M., et al. (2015) · PLOS Medicine · doi:10.1371/journal.pmed.1001779 · Cited by 12,728 · see citing works
Second-generation PLINK: rising to the challenge of larger and richer datasets
Chang, C. C., Chow, C. C., Tellier, L. C., Vattikuti, S., Purcell, S. M., & Lee, J. J. (2015) · Gigascience · doi:10.1186/s13742-015-0047-8 · Cited by 12,709 · see citing works
Finding the missing heritability of complex diseases
Manolio, T. A., Collins, F. S., Cox, N. J., Goldstein, D. B., Hindorff, L. A., Hunter, D. J., McCarthy, M. I., Ramos, E. M., Cardon, L. R., Chakravarti, A., et al. (2009) · Nature · doi:10.1038/nature08494 · Cited by 8,336 · see citing works
Self-citationGCTA: a tool for genome-wide complex trait analysis
Yang, J., Lee, S. H., Goddard, M. E., & Visscher, P. M. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.11.011 · Cited by 8,279 · see citing works
Self-citationAn integrated map of genetic variation from 1,092 human genomes
The 1000 Genomes Project Consortium (2012) · Nature · doi:10.1038/nature11632 · Cited by 7,711 · see citing works
Biological insights from 108 schizophrenia-associated genetic loci
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) · Nature · doi:10.1038/nature13595 · Cited by 7,577 · see citing works
Self-citationThe Pfam protein families database: towards a more sustainable future
Finn, R. D., Coggill, P., Eberhardt, R. Y., Eddy, S. R., Mistry, J., Mitchell, A. L., Potter, S. C., Punta, M., Qureshi, M., Sangrador-Vegas, A., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1344 · Cited by 5,975 · see citing works
Genetic studies of body mass index yield new insights for obesity biology
Study, T. L. C., Locke, A. E., The ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The, G. L. G. C., The, I. C. B. P., The MAGIC Investigators, The MuTHER Consortium, et al. (2015) · Nature · doi:10.1038/nature14177 · Cited by 4,534 · see citing works
Self-citationCommon SNPs explain a large proportion of the heritability for human height
Yang, J., Benyamin, B., McEvoy, B. P., Gordon, S., Henders, A. K., Nyholt, D. R., Madden, P. A., Heath, A. C., Martin, N. G., Montgomery, G. W., et al. (2010) · Nature Genetics · doi:10.1038/ng.608 · Cited by 4,446 · see citing works
Self-citationAn atlas of genetic correlations across human diseases and traits
ReproGen Consortium, Bulik-Sullivan, B., Psychiatric Genomics Consortium, Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control Consortium 3, Finucane, H. K., Anttila, V., Gusev, A., Day, F. R., Loh, P.-R., Duncan, L., et al. (2015) · Nature Genetics · doi:10.1038/ng.3406 · Cited by 4,255 · see citing works
10 Years of GWAS Discovery: Biology, Function, and Translation
Visscher, P. M., Wray, N. R., Zhang, Q., Sklar, P., McCarthy, M. I., Brown, M. A., & Yang, J. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.06.005 · Cited by 3,719 · see citing works
Self-citationThe hitch-hiking effect of a favourable gene
Smith, J. M., & Haigh, J. (1974) · Genetical Research · doi:10.1017/s0016672300014634 · Cited by 3,415 · see citing works
Integrating common and rare genetic variation in diverse human populations
The International HapMap 3 Consortium (2010) · Nature · doi:10.1038/nature09298 · Cited by 3,026 · see citing works
(2013) · The Lancet · doi:10.1016/s0140-6736(12)62129-1 · Cited by 3,010 · see citing works
A reference panel of 64,976 haplotypes for genotype imputation
the Haplotype Reference Consortium (2016) · Nature Genetics · doi:10.1038/ng.3643 · Cited by 2,836 · see citing works
The hitch-hiking effect of a favourable gene
MAYNARD, J., & Haigh, J. (2007) · Genetics Research · doi:10.1017/s0016672308009579 · Cited by 2,663 · see citing works
MCMC Using Hamiltonian Dynamics
Neal, R. M. (2011) · Handbook of Markov Chain Monte Carlo · doi:10.1201/b10905-6 · Cited by 2,574 · see citing works
The Electronic Medical Records and Genomics (eMERGE) Consortium, Wood, A. R., The MIGen Consortium, The PAGE Consortium, Study, T. L. C., Esko, T., Yang, J., Vedantam, S., Pers, T. H., Gustafsson, S., et al. (2014) · Nature Genetics · doi:10.1038/ng.3097 · Cited by 1,853 · see citing works
Self-citationGenome-wide patterns of selection in 230 ancient Eurasians
Mathieson, I., Lazaridis, I., Rohland, N., Mallick, S., Patterson, N., Roodenberg, S. A., Harney, E., Stewardson, K., Fernandes, D., Novak, M., et al. (2015) · Nature · doi:10.1038/nature16152 · Cited by 1,515 · see citing works
Extension of the bayesian alphabet for genomic selection
Habier, D., Fernando, R. L., Kızılkaya, K., & Garrick, D. J. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-186 · Cited by 1,234 · see citing works
Are Rare Variants Responsible for Susceptibility to Complex Diseases?
Pritchard, J. K. (2001) · The American Journal of Human Genetics · doi:10.1086/321272 · Cited by 1,197 · see citing works
de Koning, L., Merchant, A. T., Pogue, J., & Anand, S. S. (2007) · European Heart Journal · doi:10.1093/eurheartj/ehm026 · Cited by 1,073 · see citing works
Estimating Missing Heritability for Disease from Genome-wide Association Studies
Lee, S. H., Wray, N. R., Goddard, M. E., & Visscher, P. M. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.02.002 · Cited by 1,064 · see citing works
Self-citationThe genetic architecture of type 2 diabetes
Fuchsberger, C., Flannick, J., Teslovich, T. M., Mahajan, A., Agarwala, V., Gaulton, K. J., Ma, C., Fontanillas, P., Moutsianas, L., McCarthy, D. J., et al. (2016) · Nature · doi:10.1038/nature18642 · Cited by 1,051 · see citing works
The UK10K project identifies rare variants in health and disease
The UK10K Consortium, Writing group, Walter, K., Min, J. L., Huang, J., Crooks, L., Memari, Y., McCarthy, S., Perry, J. R. B., Xu, C., et al. (2015) · Nature · doi:10.1038/nature14962 · Cited by 1,040 · see citing works
Data and Theory Point to Mainly Additive Genetic Variance for Complex Traits
Hill, W. G., Goddard, M. E., & Visscher, P. M. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000008 · Cited by 1,039 · see citing works
Self-citationThe genetics of human adaptation: hard sweeps, soft sweeps, and polygenic adaptation
Pritchard, J. K., Pickrell, J. K., & Coop, G. (2010) · Current Biology · doi:10.1016/j.cub.2009.11.055 · Cited by 932 · see citing works
Genic Intolerance to Functional Variation and the Interpretation of Personal Genomes
Petrovski, S., Wang, Q., Heinzen, E. L., Allen, A. S., & Goldstein, D. B. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003709 · Cited by 901 · see citing works
Whole-Genome Regression and Prediction Methods Applied to Plant and Animal Breeding
Campos, G. D. L., Hickey, J. M., Pong‐Wong, R., Daetwyler, H. D., & Calus, M. P. L. (2012) · Genetics · doi:10.1534/genetics.112.143313 · Cited by 898 · see citing works
Genome partitioning of genetic variation for complex traits using common SNPs
Yang, J., Manolio, T. A., Pasquale, L. R., Boerwinkle, E., Caporaso, N., Cunningham, J. M., de Andrade, M., Feenstra, B., Feingold, E., Hayes, M. G., et al. (2011) · Nature Genetics · doi:10.1038/ng.823 · Cited by 890 · see citing works
Self-citationPolygenic Modeling with Bayesian Sparse Linear Mixed Models
Zhou, X., Carbonetto, P. S., & Stephens, M. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003264 · Cited by 801 · see citing works
Natural selection on protein-coding genes in the human genome
Bustamante, C. D., Fledel-Alon, A., Williamson, S., Nielsen, R., Hubisz, M. J., Glanowski, S., Tanenbaum, D. M., White, T. J., Sninsky, J. J., Hernandez, R. D., et al. (2005) · Nature · doi:10.1038/nature04240 · Cited by 788 · see citing works
Hyde, C. L., Nagle, M. W., Tian, C., Chen, X., Paciga, S. A., Wendland, J. R., Tung, J. Y., Hinds, D. A., Perlis, R. H., & Winslow, A. R. (2016) · Nature Genetics · doi:10.1038/ng.3623 · Cited by 784 · see citing works
Study, T. L. C., Yang, J., Bakshi, A., Zhu, Z., Hemani, G., Vinkhuyzen, A. A. E., Lee, S. H., Robinson, M. R., Perry, J. R. B., Nolte, I. M., et al. (2015) · Nature Genetics · doi:10.1038/ng.3390 · Cited by 745 · see citing works
Self-citationImproved Heritability Estimation from Genome-wide SNPs
Speed, D., Hemani, G., Johnson, M. R., & Balding, D. J. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.10.010 · Cited by 700 · see citing works
Efficient Coalescent Simulation and Genealogical Analysis for Large Sample Sizes
Kelleher, J., Etheridge, A. M., & McVean, G. (2016) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004842 · Cited by 660 · see citing works
Berndt, S. I., Gustafsson, S., Mägi, R., Ganna, A., Wheeler, E., Feitosa, M. F., Justice, A. E., Monda, K. L., Croteau-Chonka, D. C., Day, F. R., et al. (2013) · Nature Genetics · doi:10.1038/ng.2606 · Cited by 646 · see citing works
Self-citationDemographic history and rare allele sharing among human populations
Gravel, S., Henn, B. M., Gutenkunst, R. N., Indap, A. R., Marth, G., Clark, A. G., Yu, F., Gibbs, R. A., The 1000 Genomes Project, Bustamante, C. D., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019276108 · Cited by 625 · see citing works
Rare and low-frequency coding variants alter human adult height
Marouli, E., Graff, M., Medina-Gomez, C., Lo, K. S., Wood, A. R., Kjaer, T. R., Fine, R. S., Lu, Y., Schurmann, C., Highland, H. M., et al. (2017) · Nature · doi:10.1038/nature21039 · Cited by 610 · see citing works
Self-citationPsaty, B. M., O'Donnell, C. J., Gudnason, V., Lunetta, K. L., Folsom, A. R., Rotter, J. I., Uitterlinden, A. G., Harris, T. B., Witteman, J. C. M., & Boerwinkle, E. (2009) · Circulation: Cardiovascular Genetics · doi:10.1161/circgenetics.108.829747 · Cited by 599 · see citing works
Gazal, S., Finucane, H. K., Furlotte, N. A., Loh, P.-R., Palamara, P. F., Liu, X., Schoech, A., Bulik-Sullivan, B., Neale, B. M., Gusev, A., et al. (2017) · Nature Genetics · doi:10.1038/ng.3954 · Cited by 525 · see citing works
A Composite of Multiple Signals Distinguishes Causal Variants in Regions of Positive Selection
Grossman, S. R., Shylakhter, I., Karlsson, E. K., Byrne, E. H., Morales, S., Frieden, G., Hostetter, E., Angelino, E., Garber, M., Zuk, O., et al. (2010) · Science · doi:10.1126/science.1183863 · Cited by 512 · see citing works
Comparative studies of gene expression and the evolution of gene regulation
Romero, I. G., Ruvinsky, I., & Gilad, Y. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3229 · Cited by 488 · see citing works
A population genetic signal of polygenic adaptation
Berg, J. J., & Coop, G. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004412 · Cited by 487 · see citing works
Widespread Genomic Signatures of Natural Selection in Hominid Evolution
McVicker, G., Gordon, D., Davis, C., & Green, P. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000471 · Cited by 456 · see citing works
Adaptation–not by sweeps alone
Pritchard, J. K., & Di Rienzo, A. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2880 · Cited by 445 · see citing works
Reevaluation of SNP heritability in complex human traits
Speed, D., Cai, N., Johnson, M. R., Nejentsev, S., & Balding, D. J. (2017) · Nature Genetics · doi:10.1038/ng.3865 · Cited by 436 · see citing works
Classic Selective Sweeps Were Rare in Recent Human Evolution
Hernandez, R. D., Kelley, J. L., Elyashiv, E., Melton, S., Auton, A., McVean, G., 1000 Genomes Project, Sella, G., & Przeworski, M. (2011) · Science · doi:10.1126/science.1198878 · Cited by 427 · see citing works
Turcot, V., Lu, Y., Highland, H. M., Schurmann, C., Justice, A. E., Fine, R. S., Bradfield, J. P., Esko, T., Giri, A., Graff, M., et al. (2017) · Nature Genetics · doi:10.1038/s41588-017-0011-x · Cited by 410 · see citing works
Self-citationThe PRACTICAL Consortium, Day, F. R., kConFab Investigators, AOCS Investigators, Scotland, G., EPIC-InterAct Consortium, Study, L. C., Ruth, K. S., Thompson, D. J., Lunetta, K. L., et al. (2015) · Nature Genetics · doi:10.1038/ng.3412 · Cited by 402 · see citing works
Self-citationDetection of human adaptation during the past 2000 years
Field, Y., Boyle, E. A., Telis, N., Gao, Z., Gaulton, K. J., Golan, D., Yengo, L., Rocheleau, G., Froguel, P., McCarthy, M. I., et al. (2016) · Science · doi:10.1126/science.aag0776 · Cited by 383 · see citing works
Self-citationMoser, G., Lee, S., Hayes, B. J., Goddard, M. E., Wray, N. R., & Visscher, P. M. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1004969 · Cited by 381 · see citing works
Self-citationDavies, G., Marioni, R. E., Liewald, D. C., Hill, W. D., Hagenaars, S. P., Harris, S. E., Ritchie, S. J., Luciano, M., Fawns-Ritchie, C., Lyall, D., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.45 · Cited by 373 · see citing works
Large-scale genomics unveils the genetic architecture of psychiatric disorders
Gratten, J., Wray, N. R., Keller, M. C., & Visscher, P. M. (2014) · Nature Neuroscience · doi:10.1038/nn.3708 · Cited by 363 · see citing works
Self-citationGuan, Y., & Stephens, M. (2011) · The Annals of Applied Statistics · doi:10.1214/11-aoas455 · Cited by 362 · see citing works
de Moor, M. H. M., van den Berg, S. M., Verweij, K. J. H., Krueger, R. F., Luciano, M., Arias Vasquez, A., Matteson, L. K., Derringer, J., Esko, T., Amin, N., et al. (2015) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2015.0554 · Cited by 345 · see citing works
Self-citationEvidence of widespread selection on standing variation in Europe at height-associated SNPs
Turchin, M. C., Chiang, C. W., Palmer, C. D., Sankararaman, S., Reich, D., Genetic Investigation of ANthropometric Traits (GIANT) Consortium, & Hirschhorn, J. N. (2012) · Nature Genetics · doi:10.1038/ng.2368 · Cited by 329 · see citing works
Theoretical models of selection and mutation on quantitative traits
Johnson, T., & Barton, N. (2005) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2005.1667 · Cited by 313 · see citing works
Park, J.-H., Gail, M. H., Weinberg, C. R., Carroll, R. J., Chung, C. C., Wang, Z., Chanock, S. J., Fraumeni, J. F., & Chatterjee, N. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1114759108 · Cited by 280 · see citing works
The deleterious mutation load is insensitive to recent population history.
Simons, Y. B., Turchin, M. C., Pritchard, J. K., & Sella, G. (2014) · Nature Genetics · doi:10.1038/ng.2896 · Cited by 279 · see citing works
The human gene damage index as a gene-level approach to prioritizing exome variants
Itan, Y., Shang, L., Boisson, B., Patin, É., Bolze, A., Moncada‐Vélez, M., Scott, E., Ciancanelli, M. J., Lafaille, F. G., Markle, J., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1518646112 · Cited by 271 · see citing works
Barbosa‐Morais, N. L., Dunning, M., Samarajiwa, S., Darot, J. F. J., Ritchie, M. E., Lynch, A. G., & Tavaré, S. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp942 · Cited by 257 · see citing works
Human adaptations to diet, subsistence, and ecoregion are due to subtle shifts in allele frequency
Hancock, A. M., Witonsky, D., Ehler, E., Alkorta‐Aranburu, G., Beall, C. M., Gebremedhin, A., Sukernik, R. I., Utermann, G., Pritchard, J. K., Coop, G., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914625107 · Cited by 255 · see citing works
The Genetic Architecture of Gene Expression in Peripheral Blood
Lloyd‐Jones, L. R., Holloway, A., McRae, A. F., Yang, J., Small, K. S., Zhao, J., Zeng, B., Bakshi, A., Metspalu, A., Dermitzakis, M., et al. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.12.008 · Cited by 243 · see citing works
Self-citationEyre‐Walker, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906182107 · Cited by 231 · see citing works
Population genetic differentiation of height and body mass index across Europe
Robinson, M. R., Hemani, G., Medina‐Gómez, C., Mezzavilla, M., Esko, T., Shakhbazov, K., Powell, J. E., Vinkhuyzen, A. A. E., Berndt, S. I., Gustafsson, S., et al. (2015) · Nature Genetics · doi:10.1038/ng.3401 · Cited by 225 · see citing works
Self-citationNatural selection on gene expression
Gilad, Y., Oshlack, A., & Rifkin, S. A. (2006) · Trends in Genetics · doi:10.1016/j.tig.2006.06.002 · Cited by 218 · see citing works
Fernando, R. L., Dekkers, J. C. M., & Garrick, D. J. (2014) · Genetics Selection Evolution · doi:10.1186/1297-9686-46-50 · Cited by 205 · see citing works
Genetic Basis of Male Pattern Baldness
Heath, A. C., Nyholt, D. R., Gillespie, N. A., & Martin, N. G. (2003) · Journal of Investigative Dermatology · doi:10.1111/j.1523-1747.2003.12615.x · Cited by 197 · see citing works
Wass, P., Waldenström, U., Rössner, S. M., & Hellberg, D. (1997) · Human Reproduction · doi:10.1093/humrep/12.9.2057 · Cited by 193 · see citing works
SLiM: Simulating Evolution with Selection and Linkage
Messer, P. W. (2013) · Genetics · doi:10.1534/genetics.113.152181 · Cited by 191 · see citing works
The Optimal Discovery Procedure: A New Approach to Simultaneous Significance Testing
Storey, J. D. (2007) · Journal of the Royal Statistical Society Series B (Statistical Methodology) · doi:10.1111/j.1467-9868.2007.005592.x · Cited by 188 · see citing works
Determinants of intra-specific variation in basal metabolic rate
Konarzewski, M., & Książek, A. (2012) · Journal of Comparative Physiology B · doi:10.1007/s00360-012-0698-z · Cited by 176 · see citing works
Selection against variants in the genome associated with educational attainment
Kong, A., Frigge, M. L., Thorleifsson, G., Stefansson, H., Young, A. I., Zink, F., Jonsdottir, G. A., Okbay, A., Sulem, P., Masson, G., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1612113114 · Cited by 168 · see citing works
Genome-wide signals of positive selection in human evolutionPreprint
Enard, D., Messer, P. W., & Petrov, D. A. (2014) · Genome Research · doi:10.1101/gr.164822.113 · Cited by 167 · see citing works
Controlling the Proportion of False Positives in Multiple Dependent Tests
Fernando, R. L., Nettleton, D. S., Southey, B. R., Dekkers, J. C. M., Rothschild, M. F., & Soller, M. (2004) · Genetics · doi:10.1534/genetics.166.1.611 · Cited by 165 · see citing works
Bayesian Methods Applied to GWAS
Fernando, R. L., & Garrick, D. J. (2013) · Methods in molecular biology · doi:10.1007/978-1-62703-447-0_10 · Cited by 154 · see citing works
Genotype–covariate interaction effects and the heritability of adult body mass index
Robinson, M. R., English, G., Moser, G., Lloyd‐Jones, L. R., Triplett, M. A., Zhu, Z., Nolte, I. M., van Vliet‐Ostaptchouk, J. V., Snieder, H., Study, T. L. C., et al. (2017) · Nature Genetics · doi:10.1038/ng.3912 · Cited by 149 · see citing works
Self-citationVisscher, P. M., Goddard, M. E., Derks, E. M., & Wray, N. R. (2012) · Molecular Psychiatry · doi:10.1038/mp.2011.65 · Cited by 138 · see citing works
Self-citationThe contribution of rare variation to prostate cancer heritability
Mancuso, N., Rohland, N., Rand, K. A., Tandon, A., Allen, A., Quinque, D., Mallick, S., Li, H., Stram, A. H., Sheng, X., et al. (2015) · Nature Genetics · doi:10.1038/ng.3446 · Cited by 137 · see citing works
Torgerson, D. G., Boyko, A. R., Hernandez, R. D., Indap, A. R., Hu, X., White, T. J., Sninsky, J. J., Cargill, M., Adams, M. D., Bustamante, C. D., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000592 · Cited by 136 · see citing works
Negative selection in humans and fruit flies involves synergistic epistasis
Sohail, M., Vakhrusheva, O. A., Sul, J. H., Pulit, S. L., Francioli, L. C., Initiative, A. D. N., van den Berg, L. H., Veldink, J. H., de Bakker, P. I. W., Bazykin, G. A., et al. (2017) · Science · doi:10.1126/science.aah5238 · Cited by 115 · see citing works
EVOLUTION OF GENETIC ARCHITECTURE UNDER DIRECTIONAL SELECTION
Hansen, T. F., Álvarez-Castro, J. M., Carter, A. J. R., Hermisson, J., & Wagner, G. P. (2006) · Evolution · doi:10.1111/j.0014-3820.2006.tb00498.x · Cited by 96 · see citing works
Estimation of SNP Heritability from Dense Genotype Data
Lee, S., Yang, J., Chen, G., Ripke, S., Stahl, E. A., Hultman, C. M., Sklar, P. B., Visscher, P. M., Sullivan, P. F., Goddard, M. E., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.10.015 · Cited by 92 · see citing works
Self-citationChen, G., Lee, S., Zhu, Z.-X., Benyamin, B., & Robinson, M. R. (2016) · Heredity · doi:10.1038/hdy.2016.25 · Cited by 75 · see citing works
Self-citationThe Distribution of Gene Frequencies in Populations of Polyploids
Wright, S. (1938) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.24.9.372 · Cited by 70 · see citing works
Leveraging Distant Relatedness to Quantify Human Mutation and Gene-Conversion Rates
Palamara, P. F., Francioli, L. C., Wilton, P., Genovese, G., Gusev, A., Finucane, H. K., Sankararaman, S., Sunyaev, S. R., de Bakker, P. I. W., Wakeley, J., et al. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.10.006 · Cited by 69 · see citing works
Casto, A. M., & Feldman, M. W. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1001266 · Cited by 66 · see citing works
Prediction of male-pattern baldness from genotypes
Liu, F., Hamer, M. A., Heilmann‐Heimbach, S., Herold, C., Moebus, S., Albert Hofman, D., Uitterlinden, A. G., Nöthen, M. M., van Duijn, C. M., Nijsten, T. E. C., et al. (2015) · European Journal of Human Genetics · doi:10.1038/ejhg.2015.220 · Cited by 65 · see citing works
Uricchio, L. H., Zaitlen, N., Ye, C., Witte, J. S., & Hernandez, R. D. (2016) · Genome Research · doi:10.1101/gr.202440.115 · Cited by 54 · see citing works
Lloyd‐Jones, L. R., Robinson, M. R., Moser, G., Zeng, J., Beleza, S. S., Barsh, G. S., Tang, H., & Visscher, P. M. (2017) · Genetics · doi:10.1534/genetics.116.193383 · Cited by 27 · see citing works
Self-citationGenotype-Specific Recurrence Risks as Indicators of the Genetic Architecture of Complex Diseases
Slatkin, M. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.06.011 · Cited by 9 · see citing works
(2014) · Journal of the American Statistical Association · doi:10.1080/01621459.2014.963405 · Cited by 9 · see citing works
Whole genome analyses accounting for structures in genotype data
Zeng, J. (2015) · doi:10.31274/etd-180810-4251 · Cited by 6 · see citing works
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Võsa, U., Claringbould, A., Westra, H.-J., Bonder, M. J., Deelen, P., Zeng, B., Kirsten, H., Saha, A., Kreuzhuber, R., Yazar, S., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00913-z · Cited by 2,607 · see citing works
Self-citationGenome-wide association studies
Uffelmann, E., Huang, Q. Q., Munung, N. S., de Vries, J., Okada, Y., Martin, A. R., Martin, H. C., Lappalainen, T., & Posthuma, D. (2021) · Nature Reviews Methods Primers · doi:10.1038/s43586-021-00056-9 · Cited by 1,849 · see citing works
Leveraging Polygenic Functional Enrichment to Improve GWAS Power
Kichaev, G., Bhatia, G., Loh, P.-R., Gazal, S., Burch, K., Freund, M. K., Schoech, A., Pasaniuc, B., & Price, A. L. (2019) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2018.11.008 · Cited by 926 · see citing works
Xue, A., Wu, Y., Zhu, Z., Zhang, F., Kemper, K. E., Zheng, Z., Yengo, L., Lloyd‐Jones, L. R., Sidorenko, J., Wu, Y., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04951-w · Cited by 884 · see citing works
Self-citationA brief history of human disease genetics
Claussnitzer, M., Cho, J. H., Collins, R., Cox, N. J., Dermitzakis, E. T., Hurles, M. E., Kathiresan, S., Kenny, E. E., Lindgren, C. M., MacArthur, D. G., et al. (2020) · Nature · doi:10.1038/s41586-019-1879-7 · Cited by 697 · see citing works
Improving polygenic prediction in ancestrally diverse populations
Ruan, Y., Lin, Y.-F., Feng, Y.-C. A., Chen, C.-Y., Lam, M., Guo, Z., Initiatives, S. G. A., Ahn, Y. M., Akiyama, K., Arai, M., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01054-7 · Cited by 707 · see citing works
Okbay, A., Wu, Y., Wang, N., Jayashankar, H., Bennett, M., Nehzati, S. M., Sidorenko, J., Kweon, H., Goldman, G., Gjorgjieva, T., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01016-z · Cited by 654 · see citing works
Self-citation15 years of GWAS discovery: Realizing the promise
Abdellaoui, A., Yengo, L., Verweij, K. J. H., & Visscher, P. M. (2023) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2022.12.011 · Cited by 542 · see citing works
Self-citationvan Rheenen, W., van der Spek, R. A. A., Bakker, M. K., van Vugt, J. J. F. A., Hop, P. J., Zwamborn, R. A. J., de Klein, N., Westra, H.-J., Bakker, O. B., Deelen, P., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00973-1 · Cited by 542 · see citing works
Improved polygenic prediction by Bayesian multiple regression on summary statistics
Lloyd-Jones, L. R., Zeng, J., Sidorenko, J., Yengo, L., Moser, G., Kemper, K. E., Wang, H., Zheng, Z., Magi, R., Esko, T., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12653-0 · Cited by 528 · see citing works
Self-citationWainschtein, P., Jain, D., Zheng, Z., TOPMed Anthropometry Working Group, Aslibekyan, S. W., Becker, D. M., Bi, W., Brody, J. A., Carlson, J. C., Correa, A., et al. (2022) · Nature Genetics · doi:10.1038/s41588-021-00997-7 · Cited by 504 · see citing works
Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation
Min, J. L., Hemani, G., Hannon, E., Dekkers, K. F., Castillo-Fernandez, J., Luijk, R., Carnero-Montoro, E., Lawson, D. J., Burrows, K., Suderman, M., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00923-x · Cited by 506 · see citing works
Self-citationDefining the genetic, genomic, cellular, and diagnostic architectures of psychiatric disorders
Sullivan, P. F., & Geschwind, D. H. (2019) · Cell · doi:10.1016/j.cell.2019.01.015 · Cited by 452 · see citing works
“0), are more likely to be deleterious, and tend to be removed by natural selection (Fu et al., 2013; Nelson et al., 2012; Zeng et al., 2018).”
BackgroundBias correction for inverse variance weighting Mendelian randomization
Mounier, N., & Kutalik, Z. (2023) · Genetic Epidemiology · doi:10.1002/gepi.22522 · Cited by 445 · see citing works
Concepts, estimation and interpretation of SNP-based heritability
Yang, J., Zeng, J., Goddard, M. E., Wray, N. R., & Visscher, P. M. (2017) · Nature Genetics · doi:10.1038/ng.3941 · Cited by 435 · see citing works
Self-citationFrei, O., Holland, D., Smeland, O. B., Shadrin, A. A., Fan, C. C., Maeland, S., O’Connell, K. S., Wang, Y., Djurovic, S., Thompson, W. K., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10310-0 · Cited by 410 · see citing works
O’Sullivan, J. W., Raghavan, S., Márquez‐Luna, C., Luzum, J. A., Damrauer, S. M., Ashley, E. A., O’Donnell, C. J., Willer, C. J., & Natarajan, P. (2022) · Circulation · doi:10.1161/cir.0000000000001077 · Cited by 424 · see citing works
Polygenic adaptation: a unifying framework to understand positive selection
Barghi, N., Hermisson, J., & Schlötterer, C. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-020-0250-z · Cited by 404 · see citing works
Functionally informed fine-mapping and polygenic localization of complex trait heritability
Weissbrod, O., Hormozdiari, F., Benner, C., Cui, R., Ulirsch, J., Gazal, S., Schoech, A. P., van de Geijn, B., Reshef, Y., Márquez-Luna, C., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-00735-5 · Cited by 364 · see citing works
Sohail, M., Maier, R. M., Ganna, A., Bloemendal, A., Martin, A. R., Turchin, M. C., Chiang, C. W., Hirschhorn, J., Daly, M. J., Patterson, N., et al. (2019) · eLife · doi:10.7554/elife.39702 · Cited by 359 · see citing works
Systematic differences in discovery of genetic effects on gene expression and complex traits
Mostafavi, H., Spence, J. P., Naqvi, S., & Pritchard, J. K. (2023) · Nature Genetics · doi:10.1038/s41588-023-01529-1 · Cited by 336 · see citing works
Quantifying genetic effects on disease mediated by assayed gene expression levels
Yao, D. W., O’Connor, L. J., Price, A. L., & Gusev, A. (2020) · Nature Genetics · doi:10.1038/s41588-020-0625-2 · Cited by 274 · see citing works
Risk prediction of late-onset Alzheimer’s disease implies an oligogenic architecture
Zhang, Q., Sidorenko, J., Couvy-Duchesne, B., Marioni, R. E., Wright, M. J., Goate, A. M., Marcora, E., Huang, K.-L., Porter, T., Laws, S. M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18534-1 · Cited by 272 · see citing works
Self-citationWang, Y., Guo, J., Ni, G., Yang, J., Visscher, P. M., & Yengo, L. (2020) · Nature Communications · doi:10.1038/s41467-020-17719-y · Cited by 271 · see citing works
Self-citationExtreme Polygenicity of Complex Traits Is Explained by Negative Selection
O'Connor, L. J., Schoech, A. P., Hormozdiari, F., Gazal, S., Patterson, N., & Price, A. L. (2019) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2019.07.003 · Cited by 268 · see citing works
Weissbrod, O., Kanai, M., Shi, H., Gazal, S., Peyrot, W. J., Khera, A. V., Okada, Y., The Biobank Japan Project, Matsuda, K., Yamanashi, Y., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01036-9 · Cited by 252 · see citing works
Andreassen, O. A., Hindley, G., Frei, O., & Smeland, O. B. (2023) · World Psychiatry · doi:10.1002/wps.21034 · Cited by 255 · see citing works
Haplotype Reference Consortium, Evans, L. M., Tahmasbi, R., Vrieze, S. I., Abecasis, G. R., Das, S., Gazal, S., Bjelland, D. W., de Candia, T. R., Goddard, M. E., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0108-x · Cited by 239 · see citing works
Self-citationHolland, D., Frei, O., Desikan, R. S., Fan, C. C., Shadrin, A. A., Smeland, O. B., Sundar, V. S., Thompson, P. M., Andreassen, O. A., & Dale, A. M. (2020) · PLoS Genetics · doi:10.1371/journal.pgen.1008612 · Cited by 229 · see citing works
Zheng, Z., Liu, S., Sidorenko, J., Wang, Y., Lin, T., Yengo, L., Turley, P., Ani, A., Wang, R., Nolte, I. M., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01704-y · Cited by 223 · see citing works
Self-citationGenomics of hypertension: the road to precision medicine
Padmanabhan, S., & Dominiczak, A. F. (2020) · Nature Reviews Cardiology · doi:10.1038/s41569-020-00466-4 · Cited by 220 · see citing works
Recovery of trait heritability from whole genome sequence data
Wainschtein, P., Jain, D., Zheng, Z., TOPMed Anthropometry Working Group, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Cupples, L. A., Shadyab, A. H., McKnight, B., Shoemaker, B. M., Mitchell, B. D., et al. (2019) · doi:10.1101/588020 · Cited by 515 · see citing works
Self-citationThe polygenic architecture of schizophrenia — rethinking pathogenesis and nosology
Smeland, O. B., Frei, O., Dale, A. M., & Andreassen, O. A. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0364-0 · Cited by 202 · see citing works
Missing heritability of complex diseases: case solved?
Génin, E. (2019) · Human Genetics · doi:10.1007/s00439-019-02034-4 · Cited by 210 · see citing works
Zhu, X., Bai, W.-Y., & Zheng, H. (2021) · Bone Research · doi:10.1038/s41413-021-00143-3 · Cited by 193 · see citing works
Evaluation of polygenic prediction methodology within a reference-standardized framework
Pain, O., Glanville, K. P., Hagenaars, S. P., Selzam, S., Fürtjes, A. E., Gaspar, H. A., Coleman, J. R. I., Rimfeld, K., Breen, G. D., Plomin, R. J., et al. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009021 · Cited by 174 · see citing works
Enhancers in disease: molecular basis and emerging treatment strategies
Claringbould, A., & Zaugg, J. B. (2021) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2021.07.012 · Cited by 171 · see citing works
Evaluating and improving heritability models using summary statistics
Speed, D., Holmes, J., & Balding, D. J. (2020) · Nature Genetics · doi:10.1038/s41588-020-0600-y · Cited by 166 · see citing works
Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk
Mitrovič, M., Patsopoulos, N. A., Beecham, A. H., Dankowski, T., Goris, A., Dubois, B., D'hooghe, M. B., Lemmens, R., Damme, P. V., Søndergaard, H. B., et al. (2018) · Cell · doi:10.1016/j.cell.2018.09.049 · Cited by 172 · see citing works
Xiang, R., van den Berg, I., MacLeod, I. M., Hayes, B. J., Prowse-Wilkins, C., Wang, M., Bolormaa, S., Liu, Z., Rochfort, S. J., Reich, C. M., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1904159116 · Cited by 171 · see citing works
Zeng, J., Xue, A., Jiang, L., Lloyd-Jones, L. R., Wu, Y., Wang, H., Zheng, Z., Yengo, L., Kemper, K. E., Goddard, M. E., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21446-3 · Cited by 144 · see citing works
Self-citationPolygenic architecture of rare coding variation across 394,783 exomes
Weiner, D. J., Nadig, A., Jagadeesh, K. A., Dey, K. K., Neale, B. M., Robinson, E., Karczewski, K. J., & O’Connor, L. J. (2023) · Nature · doi:10.1038/s41586-022-05684-z · Cited by 160 · see citing works
Gazal, S., Loh, P.-R., Finucane, H. K., Ganna, A., Schoech, A., Sunyaev, S., & Price, A. L. (2018) · Nature Genetics · doi:10.1038/s41588-018-0231-8 · Cited by 154 · see citing works
Fabbri, C., Hagenaars, S. P., John, C., Williams, A. T., Shrine, N. R. G., Moles, L., Hanscombe, K. B., Serretti, A., Shepherd, D. J., Free, R. C., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01062-9 · Cited by 156 · see citing works
Schoech, A. P., Jordan, D. M., Loh, P.-R., Gazal, S., O’Connor, L. J., Balick, D. J., Palamara, P. F., Finucane, H. K., Sunyaev, S. R., & Price, A. L. (2019) · Nature Communications · doi:10.1038/s41467-019-08424-6 · Cited by 157 · see citing works
Márquez‐Luna, C., Gazal, S., Loh, P., Kim, S. S., Furlotte, N. A., Auton, A., Agee, M., Alipanahi, B., Bell, R. K., Bryc, K., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25171-9 · Cited by 148 · see citing works
Baselmans, B. M. L., Yengo, L., van Rheenen, W., & Wray, N. R. (2021) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.05.034 · Cited by 132 · see citing works
Self-citationZhang, Y., Hurson, A. N., Zhang, H., Choudhury, P. P., Easton, D. F., Milne, R. L., Simard, J., Hall, P. N., Michailidou, K., Dennis, J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16483-3 · Cited by 134 · see citing works
Ding, Y., Hou, K., Burch, K. S., Lapinska, S., Privé, F., Vilhjálmsson, B. J., Sankararaman, S., & Paşaniuc, B. (2021) · Nature Genetics · doi:10.1038/s41588-021-00961-5 · Cited by 136 · see citing works
Identifying the Common Genetic Basis of Antidepressant Response
Pain, O., Hodgson, K., Trubetskoy, V., Ripke, S., Marshe, V. S., Adams, M. J., Byrne, E. M., Campos, A. I., Carrillo‐Roa, T., Cattaneo, A., et al. (2021) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2021.07.008 · Cited by 128 · see citing works
Self-citationDissection of genetic variation and evidence for pleiotropy in male pattern baldness
Yap, C. X., Sidorenko, J., Wu, Y., Kemper, K. E., Yang, J., Wray, N. R., Robinson, M. R., & Visscher, P. M. (2018) · Nature Communications · doi:10.1038/s41467-018-07862-y · Cited by 124 · see citing works
Self-citationHou, K., Ding, Y., Xu, Z., Wu, Y., Bhattacharya, A., Mester, R., Belbin, G. M., Buyske, S. G., Conti, D. V., Darst, B. F., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01338-6 · Cited by 113 · see citing works
Self-citationLeveraging base-pair mammalian constraint to understand genetic variation and human disease
Sullivan, P. F., Meadows, J. R. S., Gazal, S., Phan, B. N., Li, X., Genereux, D. P., Dong, M. X., Bianchi, M., Andrews, G., Sakthikumar, S., et al. (2023) · Science · doi:10.1126/science.abn2937 · Cited by 110 · see citing works
Self-citationQian, J., Tanigawa, Y., Du, W., Aguirre, M., Chang, C. C., Tibshirani, R. J., Rivas, M. A., & Hastie, T. J. (2020) · PLoS Genetics · doi:10.1371/journal.pgen.1009141 · Cited by 116 · see citing works
Fan, H., Jamsandekar, M., Pettersson, M. E., Su, L., Fuentes‐Pardo, A. P., Davis, B. W., Bekkevold, D., Berg, F., Casini, M., Dahle, G., et al. (2020) · eLife · doi:10.7554/elife.61076 · Cited by 112 · see citing works
Shi, H., Gazal, S., Kanai, M., Koch, E. M., Schoech, A. P., Siewert, K. M., Kim, S. S., Luo, Y., Amariuta, T., Huang, H., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21286-1 · Cited by 119 · see citing works
Gidziela, A., Ahmadzadeh, Y. I., Michelini, G., Allegrini, A. G., Agnew‐Blais, J. C., Lau, L. Y., Duret, M., Procopio, F., Daly, E., Ronald, A., et al. (2023) · Nature Human Behaviour · doi:10.1038/s41562-023-01530-y · Cited by 125 · see citing works
Pleiotropy, epistasis and the genetic architecture of quantitative traits
Mackay, T. F. C., & Anholt, R. R. H. (2024) · Nature Reviews Genetics · doi:10.1038/s41576-024-00711-3 · Cited by 117 · see citing works
Ultrarare variants drive substantial cis heritability of human gene expression
Hernandez, R. D., Uricchio, L. H., Hartman, K., Ye, C., Dahl, A., & Zaitlen, N. (2019) · Nature Genetics · doi:10.1038/s41588-019-0487-7 · Cited by 116 · see citing works
Polygenic adaptation after a sudden change in environment
Hayward, L. K., & Sella, G. (2022) · eLife · doi:10.7554/elife.66697 · Cited by 115 · see citing works
Peyrot, W. J., & Price, A. L. (2021) · Nature Genetics · doi:10.1038/s41588-021-00787-1 · Cited by 106 · see citing works
Human Disease Variation in the Light of Population Genomics
Prohaska, A., Racimo, F., Schork, A. J., Sikora, M., Stern, A. J., Ilardo, M. A., Allentoft, M. E., Folkersen, L., Buil, A., Moreno-Mayar, J. V., et al. (2019) · Cell · doi:10.1016/j.cell.2019.01.052 · Cited by 108 · see citing works
Cai, M., Xiao, J., Zhang, S., Wan, X., Zhao, H., Chen, G., & Yang, C. (2021) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2021.03.002 · Cited by 100 · see citing works
Shi, H., Burch, K. S., Johnson, R., Freund, M. K., Kichaev, G., Mancuso, N., Manuel, A. M., Dong, N., & Paşaniuc, B. (2020) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2020.04.012 · Cited by 87 · see citing works
Statistical methods for SNP heritability estimation and partition: A review
Zhu, H., & Zhou, X. (2020) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2020.06.011 · Cited by 95 · see citing works
Global genetic differentiation of complex traits shaped by natural selection in humans
Guo, J., Wu, Y., Zhu, Z., Zheng, Z., Trzaskowski, M., Zeng, J., Robinson, M. R., Visscher, P. M., & Yang, J. (2018) · Nature Communications · doi:10.1038/s41467-018-04191-y · Cited by 87 · see citing works
Self-citationAccurate estimation of SNP-heritability from biobank-scale data irrespective of genetic architecture
Hou, K., Burch, K. S., Majumdar, A., Shi, H., Mancuso, N., Wu, Y., Sankararaman, S., & Pasaniuc, B. (2019) · Nature Genetics · doi:10.1038/s41588-019-0465-0 · Cited by 91 · see citing works
Self-citationInferring disease architecture and predictive ability with LDpred2-auto
Privé, F., Albiñana, C., Arbel, J., Paşaniuc, B., & Vilhjálmsson, B. J. (2023) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2023.10.010 · Cited by 89 · see citing works
Limited overlap of eQTLs and GWAS hits due to systematic differences in discoveryPreprint
Mostafavi, H., Spence, J. P., Naqvi, S., & Pritchard, J. K. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.05.07.491045 · Cited by 86 · see citing works
Hujoel, M. L. A., Gazal, S., Hormozdiari, F., van de Geijn, B., & Price, A. L. (2019) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2019.02.008 · Cited by 80 · see citing works
van den Berg, I., Xiang, R., Jenko, J., Pausch, H., Boussaha, M., Schrooten, C., Tribout, T., Gjuvsland, A. B., Boichard, D., Nordbø, Ø., et al. (2020) · Genetics Selection Evolution · doi:10.1186/s12711-020-00556-4 · Cited by 82 · see citing works
The distribution of common-variant effect sizes
O’Connor, L. J. (2021) · Nature Genetics · doi:10.1038/s41588-021-00901-3 · Cited by 81 · see citing works
Rare penetrant mutations confer severe risk of common diseases
Fiziev, P. P., McRae, J. F., Ulirsch, J. C., Dron, J. S., Hamp, T., Yang, Y., Wainschtein, P., Ni, Z., Schraiber, J. G., Gao, H. C., et al. (2023) · Science · doi:10.1126/science.abo1131 · Cited by 73 · see citing works
Meisner, A., Kundu, P., Zhang, Y., Lan, L. V., Kim, S., Ghandwani, D., Choudhury, P. P., Berndt, S., Freedman, N., García-Closas, M., et al. (2020) · American Journal of Human Genetics · doi:10.1016/j.ajhg.2020.07.002 · Cited by 66 · see citing works
Estimating cross‐population genetic correlations of causal effect sizes
Galinsky, K. J., Reshef, Y. A., Finucane, H. K., Loh, P., Zaitlen, N., Patterson, N. J., Brown, B. C., & Price, A. L. (2019) · Genetic Epidemiology · doi:10.1002/gepi.22173 · Cited by 75 · see citing works
Badini, I., Coleman, J. R. I., Hagenaars, S. P., Hotopf, M. H., Breen, G. D., Lewis, C. M., & Fabbri, C. (2020) · Psychological Medicine · doi:10.1017/s0033291720002342 · Cited by 74 · see citing works
Detecting the genomic signal of polygenic adaptation and the role of epistasis in evolution
Csilléry, K., Rodríguez‐Verdugo, A., Rellstab, C., & Guillaume, F. (2018) · Molecular Ecology · doi:10.1111/mec.14499 · Cited by 73 · see citing works
Utility of polygenic embryo screening for disease depends on the selection strategy
Lencz, T., Backenroth, D., Granot‐Hershkovitz, E., Green, A., Gettler, K., Cho, J. H., Weissbrod, O., Zuk, O., & Carmi, S. (2021) · eLife · doi:10.7554/elife.64716 · Cited by 73 · see citing works
Discovery of genomic loci of the human cerebral cortex using genetically informed brain atlases
Makowski, C., van der Meer, D., Dong, W., Wang, H., Wu, Y., Zou, J., Liu, C., Rosenthal, S. B., Hagler, D. J., Fan, C. C., et al. (2022) · Science · doi:10.1126/science.abe8457 · Cited by 69 · see citing works
Self-citationA scalable variational inference approach for increased mixed-model association power
Loya, H., Kalantzis, G., Cooper, F., & Palamara, P. F. (2025) · Nature Genetics · doi:10.1038/s41588-024-02044-7 · Cited by 75 · see citing works
Yuan, X.-B., Jiang, X., Zhang, M., Wang, L., Wu, J., Chen, H., Mao, J., Ye, W., & Song, Q. (2024) · The Plant Cell · doi:10.1093/plcell/koae062 · Cited by 70 · see citing works
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Enbody, E. D., Sendell-Price, A. T., Sprehn, C. G., Rubin, C.-J., Visscher, P. M., Grant, B. R., Grant, P. R., & Andersson, L. (2023) · Science · doi:10.1126/science.adf6218 · Cited by 69 · see citing works
Self-citationInferring Gene-by-Environment Interactions with a Bayesian Whole-Genome Regression Model
Kerin, M., & Marchini, J. (2020) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2020.08.009 · Cited by 69 · see citing works
Evidence for Weak Selective Constraint on Human Gene Expression
Glassberg, E. C., Gao, Z., Harpak, A., Lan, X., & Pritchard, J. K. (2018) · Genetics · doi:10.1534/genetics.118.301833 · Cited by 63 · see citing works
Yu, Z., Jin, J., Tin, A., Köttgen, A., Yu, B., Chen, J., Surapaneni, A., Zhou, L., Ballantyne, C. M., Hoogeveen, R. C., et al. (2021) · Journal of the American Society of Nephrology · doi:10.1681/asn.2020111599 · Cited by 64 · see citing works
mBAT-combo: A more powerful test to detect gene-trait associations from GWAS data
Li, A., Liu, S., Bakshi, A., Jiang, L., Chen, W., Zheng, Z., Sullivan, P. F., Visscher, P. M., Wray, N. R., Yang, J., et al. (2023) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2022.12.006 · Cited by 63 · see citing works
Self-citationMeier, M. A., Xu, G., Lopez‐Guerrero, M., Li, G., Smith, C., Sigmon, B., Herr, J. R., Alfano, J. R., Ge, Y., Schnable, J. C., et al. (2022) · eLife · doi:10.7554/elife.75790 · Cited by 58 · see citing works
Self-citationHoggart, C. J., Choi, S. W., García‐González, J., Souaiaia, T., Preuss, M. H., & O’Reilly, P. F. (2023) · Nature Genetics · doi:10.1038/s41588-023-01583-9 · Cited by 63 · see citing works
Negative selection on complex traits limits phenotype prediction accuracy between populations
Durvasula, A., & Lohmueller, K. E. (2021) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2021.02.013 · Cited by 57 · see citing works
Disentangling selection on genetically correlated polygenic traits via whole-genome genealogies
Stern, A. J., Speidel, L., Zaitlen, N., & Nielsen, R. (2021) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2020.12.005 · Cited by 57 · see citing works
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Passamonti, M. M., Somenzi, E., Barbato, M., Chillemi, G., Colli, L., Joost, S., Milanesi, M., Negrini, R., Santini, M., Vajana, E., et al. (2021) · Animals · doi:10.3390/ani11102833 · Cited by 60 · see citing works
Interpreting Behavior Genetic Models: Seven Developmental Processes to Understand
Briley, D., Livengood, J., Derringer, J., Tucker-Drob, E., Fraley, R. C., & Roberts, B. (2018) · Behavior Genetics · doi:10.1007/s10519-018-9939-6 · Cited by 43 · see citing works
Milesi, P., Berlin, M., Chen, J., Orsucci, M., Li, L., Jansson, G., Karlsson, B., & Lascoux, M. (2019) · Evolutionary Applications · doi:10.1111/eva.12855 · Cited by 55 · see citing works
Limitations of principal components in quantitative genetic association models for human studies
Yao, Y., & Ochoa, A. (2023) · eLife · doi:10.7554/elife.79238 · Cited by 54 · see citing works
de Miguel, M., Rodríguez‐Quilón, I., Heuertz, M., Hurel, A., Grivet, D., Jaramillo‐Correa, J. P., VENDRAMIN, G. G., Plomion, C., Majada, J. P., Alı́a, R., et al. (2022) · Molecular Ecology · doi:10.1111/mec.16367 · Cited by 54 · see citing works
Wientjes, Y. C. J., Bijma, P., Calus, M. P. L., Zwaan, B. J., Vitezica, Z. G., & van den Heuvel, J. (2022) · Genetics Selection Evolution · doi:10.1186/s12711-022-00709-7 · Cited by 52 · see citing works
Márquez‐Luna, C., Gazal, S., Loh, P., Kim, S. S., Furlotte, N. A., Auton, A., & Price, A. L. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/375337 · Cited by 49 · see citing works
The evolution of group differences in changing environments
Harpak, A., & Przeworski, M. (2021) · PLOS Biology · doi:10.1371/journal.pbio.3001072 · Cited by 50 · see citing works
Inferring the Nature of Missing Heritability in Human Traits Using Data from the GWAS Catalog
López‐Cortegano, E., & Caballero, A. (2019) · Genetics · doi:10.1534/genetics.119.302077 · Cited by 44 · see citing works
Biological relevance of computationally predicted pathogenicity of noncoding variants
Liu, L., Sanderford, M. D., Patel, R., Chandrashekar, P. B., Gibson, G. C., & Kumar, S. (2019) · Nature Communications · doi:10.1038/s41467-018-08270-y · Cited by 44 · see citing works
Self-citation
- Authors
- Zeng, J., de Vlaming, R., Wu, Y., Robinson, M. R., Lloyd-Jones, L. R., Yengo, L., Yap, C. X., Xue, A., Sidorenko, J., McRae, A. F., Powell, J. E., Montgomery, G. W., Metspalu, A., Esko, T., Gibson, G., Wray, N. R., Visscher, P. M., & Yang, J.
- Affiliations
- The University of Queensland (AU)
- University of Tartu (EE)
- Georgia Institute of Technology (US)
- Corresponding author
- Yang, Jian
- ORCID
- Venue
- Nature Genetics
- Published
- 2018-04-16
- Volume
- 50
- Issue
- 5
- Pages
- 746-753
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2797293309
- Cited by
- 391
- References
- 99
- Citations by year
- 2026: 38 · 2025: 51 · 2024: 43 · 2023: 50 · 2022: 46 · 2021: 63 · 2020: 42 · 2019: 30 · 2018: 23 · 2017: 4
- FWCI
- 24.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion, other-oa)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- University of Queensland
- National Institutes of Health (GM 099568, AG042568)
- Medical Research Council (1107258, 1113400, 1078037, 1078901, MC_PC_17228)
- Australian Research Council (DP160103860, DP160101343, DP160102400, 1046880, 1113400, DP160101056)
- National Health and Medical Research Council (1083656, 1078399, 1113400, 1078901, 1107258, 1078037, 1046880)
- National Institute of Mental Health (R01MH100141)
- National Institute of General Medical Sciences (P01GM099568)
- National Institute of Environmental Health Sciences (R21ES025052)
- H2020 European Research Council (647648)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Keywords
- negative selection, purifying selection, genetic architecture, complex traits, polygenicity, SNP-based heritability, natural selection signatures, educational attainment, anthropometric traits, cardiovascular traits, reproductive traits, UK Biobank
- MeSH terms
- Bayes Theorem, Gene Frequency, Genotype, Humans, Models, Genetic, Phenotype, Selection, Genetic, Linear Models, Quantitative Trait, Heritable, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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