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Finding the missing heritability of complex diseases
Open accessAbstract
Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture. Most variants identified so far confer relatively small increments in risk, and explain only a small proportion of familial clustering, leading many to question how the remaining, 'missing' heritability can be explained. Here we examine potential sources of missing heritability and propose research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.
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“In any case, these variants explain only a small proportion of total genetic risk ( 11 ).”
From β-Cell Failure in Type 2 Diabetes: Postulated Mechanisms and Prospects for Prevention and Treatment (2014) · cites this paper as [11]
In the citing paper
“the causal genetic variants thus far identified generally confer less risk than expected from empirical estimates of heritability6.”
From Genome-wide detection of tandem DNA repeats that are expanded in autism (2020) · cites this paper as [6]
In the citing paper
“The disparity between the observed effects of the variants first identified by GWAS and estimates of overall trait heritability (the ‘missing heritability’ conundrum) is now largely resolved47.”
From A brief history of human disease genetics (2020) · cites this paper as [47]
In the citing paper
“loci detected by GWAS almost without exception explain a small minority of the inferred genetic variance5,6”
From Rare and common variants: twenty arguments (2012) · cites this paper as [6]
In the citing paper
“When GWAS began the field was dominated by the simple common disease-common variant (CD-CV) hypothesis1–4 has been refuted in light of the so-called ‘missing heritability problem’”
From Rare and common variants: twenty arguments (2012) · cites this paper as [6]
In the citing paper
“While there has been a very public focus on the failure of GWAS to find the missing heritability5,6, the simplest explanation for this is that the expectations were based on unrealistic prior assumption of effect sizes.”
From Rare and common variants: twenty arguments (2012) · cites this paper as [6]
In the citing paper
“Despite the success of genome wide association (GWA) studies in identifying common single nucleotide variants (SNVs) that contribute to complex diseases1, the vast majority of genetic variants contributing to disease susceptibility are yet to be discovered.”
From Statistical analysis strategies for association studies involving rare variants (2010) · cites this paper as [2]
In the citing paper
“Using a model that assumes an underlying normally distributed but unobserved disease risk score or liability49, the nineteen loci described here account for between 10% (if AMD prevalence is close to 1%) and 30% (if AMD prevalence is closer to 10%) of the variability in disease risk (corresponding to 15–65% of the total genetic contribution to AMD).”
From Seven new loci associated with age-related macular degeneration (2013) · cites this paper as [48]
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Citations
Cites
Introduction to Quantitative Genetics.
Edwards, A. W. F., & Falconer, D. S. (1982) · Biometrics · doi:10.2307/2529912 · Cited by 21,447
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429
Self-citationPrediction of Total Genetic Value Using Genome-Wide Dense Marker Maps
Meuwissen, T. H. E., Hayes, B. J., & Goddard, M. E. (2001) · Genetics · doi:10.1093/genetics/157.4.1819 · Cited by 7,917
The Future of Genetic Studies of Complex Human Diseases
Risch, N., & Merikangas, K. (1996) · Science · doi:10.1126/science.273.5281.1516 · Cited by 5,355
A second generation human haplotype map of over 3.1 million SNPs
The International HapMap Consortium (2007) · Nature · doi:10.1038/nature06258 · Cited by 4,438
Hindorff, L. A., Sethupathy, P., Junkins, H. A., Ramos, E. M., Mehta, J. P., Collins, F. S., & Manolio, T. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903103106 · Cited by 4,013
Self-citationGenome-wide association studies for complex traits: consensus, uncertainty and challenges
McCarthy, M. I., Abecasis, G. R., Cardon, L. R., Goldstein, D. B., Little, J., Ioannidis, J. P. A., & Hirschhorn, J. N. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2344 · Cited by 2,891
Self-citationStrong association of de novo copy number mutations with autism
Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., Yamrom, B., Yoon, S., Krasnitz, A., Kendall, J., et al. (2007) · Science · doi:10.1126/science.1138659 · Cited by 2,795
Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease
the NIDDK IBD Genetics Consortium, Barrett, J. C., the Belgian-French IBD Consortium, the Wellcome Trust Case Control Consortium, Hansoul, S., Nicolae, D. L., Cho, J. H., Duerr, R. H., Rioux, J. D., Brant, S. R., et al. (2008) · Nature Genetics · doi:10.1038/ng.175 · Cited by 2,593
Self-citationMcDonald-McGinn, D. M., Sullivan, K. E., Marino, B., Philip, N., Swillen, A., Vorstman, J. A. S., Zackai, E. H., Emanuel, B. S., Vermeesch, J. R., Morrow, B. E., et al. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.71 · Cited by 2,236
Research works printed but not linked: 1
- Zeggini, E. et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nature Genet. 40, 638–645 (2008) · DOI · Paper page
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Pei, Y., Liu, Y., Yang, X., Zhang, H., Feng, G.-J., Wei, X., & Zhang, L. (2020) · Communications Biology · doi:10.1038/s42003-020-01334-0 · Cited by 273
Rossier, B. C., Baker, M. E., & Studer, R. A. (2015) · Physiological Reviews · doi:10.1152/physrev.00011.2014 · Cited by 269
Revealing the genetic structure of a trait by sequencing a population under selectionPreprint
Parts, L., Cubillos, F. A., Warringer, J., Jain, K., Salinas, F., Bumpstead, S. J., Molin, M., Zia, A., Simpson, J. T., Quail, M. A., et al. (2011) · Genome Research · doi:10.1101/gr.116731.110 · Cited by 269
Holloway, J. W., Yang, I. A., & Holgate, S. T. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.10.071 · Cited by 280
Precision nutrition for prevention and management of type 2 diabetes
Wang, D. D., & Hu, F. B. (2018) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(18)30037-8 · Cited by 281
Galarneau, G., Palmer, C. D., Sankaran, V. G., Orkin, S. H., Hirschhorn, J. N., & Lettre, G. (2010) · Nature Genetics · doi:10.1038/ng.707 · Cited by 273
Thinking About the Evolution of Complex Traits in the Era of Genome-Wide Association Studies
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Siroux, V., Basagaña, X., Boudier, A., Pin, I., García‐Aymerich, J., Vesin, A., Slama, R., Jarvis, D., Anto, J. M., Kauffmann, F., et al. (2011) · European Respiratory Journal · doi:10.1183/09031936.00120810 · Cited by 268
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Eeles, R. A., Goh, C. L., Castro, E., Bancroft, E. K., Guy, M., Olama, A. A. A., Easton, D. F., & Kote‐Jarai, Z. (2013) · Nature Reviews Urology · doi:10.1038/nrurol.2013.266 · Cited by 272
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Gutiérrez‐Arcelus, M., Rich, S. S., & Raychaudhuri, S. (2015) · Nature Reviews Genetics · doi:10.1038/nrg.2015.33 · Cited by 256
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Rosendorff, C., Lackland, D. T., Allison, M., Aronow, W. S., Black, H. R., Blumenthal, R. S., Cannon, C. P., de Lemos, J. A., Elliott, W. J., Findeiss, L., et al. (2015) · Circulation · doi:10.1161/cir.0000000000000207 · Cited by 269
Beyond Missing Heritability: Prediction of Complex Traits
Makowsky, R., Pajewski, N. M., Klimentidis, Y. C., Vazquez, A. I., Duarte, C. W., Allison, D. B., & Campos, G. D. L. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002051 · Cited by 260
The Heritability of Prostate Cancer in the Nordic Twin Study of Cancer
Hjelmborg, J., Scheike, T., Holst, K. K., Skytthe, A., Penney, K. L., Graff, R. E., Pukkala, ., Christensen, K., Adami, H., Holm, N. V., et al. (2014) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-13-0568 · Cited by 274
Quantitative Resistance: More Than Just Perception of a Pathogen
Corwin, J., & Kliebenstein, D. J. (2017) · The Plant Cell · doi:10.1105/tpc.16.00915 · Cited by 269
Pacific biosciences sequencing technology for genotyping and variation discovery in human data
Carneiro, M. O., Russ, C., Ross, M. G., Gabriel, S., Nusbaum, C., & DePristo, M. A. (2012) · BMC Genomics · doi:10.1186/1471-2164-13-375 · Cited by 255
Cellular and molecular mechanisms of allergic asthma
Komlósi, Z. I., van de Veen, W., Kovács, N., Szűcs, G., Sokołowska, M., O’Mahony, L., Akdiş, M., & Akdiş, C. A. (2021) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2021.100995 · Cited by 271
Genomic Medicine–Progress, Pitfalls, and Promise
Shendure, J., Findlay, G. M., & Snyder, M. W. (2019) · Cell · doi:10.1016/j.cell.2019.02.003 · Cited by 263
Marinko, J. T., Huang, H., Penn, W. D., Capra, J. A., Schlebach, J. P., & Sanders, C. R. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00532 · Cited by 257
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Wei, Z., Wang, W., Hu, P., Lyon, G. J., & Hakonarson, H. H. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr599 · Cited by 258
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Anstee, Q. M., Seth, D., & Day, C. P. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.01.037 · Cited by 254
DNA methylation: A mechanism for embedding early life experiences in the genome
Szyf, M., & Bick, J. (2013) · Child Development · doi:10.1111/j.1467-8624.2012.01793.x · Cited by 251
Toll‐like receptor polymorphism in host immune response to infectious diseases: A review
Mukherjee, S., Huda, S., & Babu, S. P. S. (2019) · Scandinavian Journal of Immunology · doi:10.1111/sji.12771 · Cited by 255
Magnani, J. W., Rienstra, M., Lin, H., Sinner, M. F., Lubitz, S. A., McManus, D. D., Dupuis, J., Ellinor, P. T., & Benjamin, E. J. (2011) · Circulation · doi:10.1161/circulationaha.111.039677 · Cited by 253
Rare variant association studies: considerations, challenges and opportunities
Auer, P. L., & Lettre, G. (2015) · Genome Medicine · doi:10.1186/s13073-015-0138-2 · Cited by 261
Genetic Factors Are Not the Major Causes of Chronic Diseases
Rappaport, S. M. (2016) · PLoS ONE · doi:10.1371/journal.pone.0154387 · Cited by 259
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Self-citationFrom monogenic to polygenic obesity: recent advances
Hinney, A., Vogel, C. I. G., & Hebebrand, J. (2010) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-010-0096-6 · Cited by 269
Fan, B., Onteru, S. K., Du, Z., Garrick, D. J., Stalder, K. J., & Rothschild, M. F. (2011) · PLoS ONE · doi:10.1371/journal.pone.0014726 · Cited by 248
Jendrzejewski, J., He, H., Radomska, H. S., Li, W., Tomšič, J., Liyanarachchi, S., Davuluri, R. V., Nagy, R. S., & de la Chapelle, A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1205654109 · Cited by 253
Andreassen, O. A., Hindley, G., Frei, O., & Smeland, O. B. (2023) · World Psychiatry · doi:10.1002/wps.21034 · Cited by 284
Dysregulation of expression correlates with rare-allele burden and fitness loss in maize
Kremling, K. A. G., Chen, S.-Y., Su, M.-H., Lepak, N. K., Romay, M. C., Swarts, K., Lü, F., Lorant, A., Bradbury, P. J., & Buckler, E. S. (2018) · Nature · doi:10.1038/nature25966 · Cited by 229
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Self-citationAllelic Skewing of DNA Methylation Is Widespread across the Genome
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Torkamani, A., Andersen, K. G., Steinhubl, S. R., & Topol, E. J. (2017) · Cell · doi:10.1016/j.cell.2017.08.007 · Cited by 253
Berghe, W. V. (2012) · Pharmacological Research · doi:10.1016/j.phrs.2012.03.007 · Cited by 245
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Zhang, Z., Ober, U., Erbe, M., Zhang, H., Gao, N., He, J., Li, J., & Simianer, H. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093017 · Cited by 255
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Meyer, T. E., Verwoert, G. C., Hwang, S., Glazer, N. L., Smith, A. V., van Rooij, F. J. A., Ehret, G., Boerwinkle, E., Felix, J. F., Leak, T. S., et al. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001045 · Cited by 247
Self-citationFerguson, L. R., Caterina, R. D., Görman, U., Allayee, H., Kohlmeier, M., Prasad, C., Choi, M. S., Curi, R., de Luis, D. A., Gil, Á., et al. (2016) · Lifestyle Genomics · doi:10.1159/000445350 · Cited by 270
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Palaniappan, L. P., Araneta, M. R. G., Assimes, T. L., Barrett-Connor, E. L., Carnethon, M. R., Criqui, M. H., Fung, G. L., Narayan, K. M. V., Patel, H. M., Taylor‐Piliae, R. E., et al. (2010) · Circulation · doi:10.1161/cir.0b013e3181f22af4 · Cited by 237
Coppola, G., Chinnathambi, S., Lee, J. J., Dombroski, B. A., Baker, M. C., Soto-Ortolaza, A. I., Lee, S. E., Klein, E., Huang, A. Y., Sears, R., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds161 · Cited by 240
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Genome-wide detection of tandem DNA repeats that are expanded in autism
Trost, B., Engchuan, W., Nguyen, C. M., Thiruvahindrapuram, B., Dolzhenko, E., Backstrom, I., Mirceta, M., Mojarad, B. A., Yin, Y., Dov, A., et al. (2020) · Nature · doi:10.1038/s41586-020-2579-z · Cited by 238
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Rizzo, J. M., & Buck, M. J. (2012) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-11-0432 · Cited by 251
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Gandal, M. J., Leppa, V., Won, H., Parikshak, N. N., & Geschwind, D. H. (2016) · Nature Neuroscience · doi:10.1038/nn.4409 · Cited by 223
Epigenetics at the crossroads between genes, environment and resilience in anxiety disorders
Schiele, M. A., & Domschke, K. (2018) · Genes, Brain and Behavior · doi:10.1111/gbb.12423 · Cited by 233
Johnston, S. E., McEwan, J. C., Pickering, N., Kijas, J., Beraldi, D., Pilkington, J. G., Pemberton, J. M., & Slate, J. (2011) · Molecular Ecology · doi:10.1111/j.1365-294x.2011.05076.x · Cited by 236
The genetics of primary open-angle glaucoma: A review
Allingham, R. R., Liu, Y., & Rhee, D. J. (2008) · Experimental Eye Research · doi:10.1016/j.exer.2008.11.003 · Cited by 243
Solving the missing heritability problem
Young, A. I. (2019) · PLoS Genetics · doi:10.1371/journal.pgen.1008222 · Cited by 246
The Spectrum of Achalasia: Lessons From Studies of Pathophysiology and High-Resolution Manometry
Kahrilas, P. J., & Boeckxstaens, G. E. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.08.038 · Cited by 236
Sarcoidosis epidemiology: recent estimates of incidence, prevalence and risk factors
Arkema, E. V., & Cozier, Y. C. (2020) · Current Opinion in Pulmonary Medicine · doi:10.1097/mcp.0000000000000715 · Cited by 233
Hierarchical Modularity and the Evolution of Genetic Interactomes across Species
Ryan, C. J., Roguev, A., Patrick, K. L., Xu, J., Jahari, H., Tong, Z., Beltrão, P., Shales, M., Qu, H., Collins, S. R., et al. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.05.028 · Cited by 238
Genotype to phenotype: lessons from model organisms for human genetics
Lehner, B. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3404 · Cited by 240
Current findings, challenges and novel approaches in human genetic susceptibility to tuberculosis
Möller, M., & Hoal, E. G. (2010) · Tuberculosis · doi:10.1016/j.tube.2010.02.002 · Cited by 239
Eyre‐Walker, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906182107 · Cited by 230
GPA: A Statistical Approach to Prioritizing GWAS Results by Integrating Pleiotropy and Annotation
Chung, D., Yang, C., Li, C., Gelernter, J. E., & Zhao, H. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004787 · Cited by 225
Xu, H. Y., Yang, W., Pérez-Andreu, V., Devidas, M., Fan, Y., Cheng, C., Pei, D., Scheet, P. A., Burchard, E. G., Eng, C. S., et al. (2013) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djt042 · Cited by 233
Paternally inherited cis-regulatory structural variants are associated with autism
Brandler, W. M., Antaki, D., Gujral, M., Kleiber, M. L., Whitney, J., Maile, M. S., Hong, O., Chapman, T. R., Tan, S., Tandon, P., et al. (2018) · Science · doi:10.1126/science.aan2261 · Cited by 209
Causes of genome instability: the effect of low dose chemical exposures in modern society
Langie, S. A. S., Koppen, G., Desaulniers, D. M., Al‐Mulla, F., Al-Temaimi, R. A., Amedei, A., Azqueta, A., Bisson, W. H., Brown, D. G., Brunborg, G., et al. (2015) · Carcinogenesis · doi:10.1093/carcin/bgv031 · Cited by 240
Understanding type 1 diabetes through genetics: advances and prospects
Polychronakos, C., & Li, Q. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3069 · Cited by 226
Genetics of coronary artery disease and myocardial infarction
Dai, X. (2016) · World Journal of Cardiology · doi:10.4330/wjc.v8.i1.1 · Cited by 230
Wang, Q., Gumus, Z. H., Colarossi, C., Memeo, L., Wang, X., Kong, C. Y., & Boffetta, P. (2022) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2022.10.002 · Cited by 239
Molecular and functional variation in iPSC-derived sensory neurons
HIPSCI Consortium, Schwartzentruber, J., Foskolou, S., Kilpinen, H., Rodrigues, J., Alasoo, K., Knights, A. J., Patel, M., Goncalves, A., Ferreira, R., et al. (2018) · Nature Genetics · doi:10.1038/s41588-017-0005-8 · Cited by 223
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Cooper, D. N. (2010) · Human Genomics · doi:10.1186/1479-7364-4-5-284 · Cited by 224
β-Cell Failure in Type 2 Diabetes: Postulated Mechanisms and Prospects for Prevention and Treatment
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Zhu, Z., Bakshi, A., Vinkhuyzen, A. A. E., Hemani, G., Lee, S. H., Nolte, I. M., van Vliet-Ostaptchouk, J. V., Snieder, H., Esko, T., Milani, L., et al. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.01.001 · Cited by 224
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Roden, D. M., Wilke, R. A., Kroemer, H. K., & Stein, C. M. (2011) · Circulation · doi:10.1161/circulationaha.109.914820 · Cited by 222
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Metadata
- Authors
- 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., Cho, J. H., Guttmacher, A. E., Kong, A., Kruglyak, L., Mardis, E., Rotimi, C. N., Slatkin, M., Valle, D., Whittemore, A. S., Boehnke, M., Clark, A. G., Eichler, E. E., Gibson, G., Haines, J. L., Mackay, T. F. C., McCarroll, S. A., & Visscher, P. M.
- Affiliations
- National Institutes of Health (US)
- University of Chicago (US)
- Duke University (US)
- Harvard University (US)
- Centre for Human Genetics (GB)
- GlaxoSmithKline (United Kingdom) (GB)
- Johns Hopkins University (US)
- Yale University (US)
- deCODE Genetics (Iceland) (IS)
- Howard Hughes Medical Institute (US)
- Washington University in St. Louis (US)
- University of California, Berkeley (US)
- Stanford University (US)
- University of Michigan (US)
- Cornell University (US)
- The University of Queensland (AU)
- Vanderbilt University (US)
- North Carolina State University (US)
- QIMR Berghofer Medical Research Institute (AU)
- Corresponding author
- Manolio, Teri A.
- ORCID
- Manolio, Teri A.
- Collins, Francis S.
- Cox, Nancy J.
- Goldstein, David B.
- Hindorff, Lucia A.
- McCarthy, Mark I.
- Ramos, Erin M.
- Chakravarti, Aravinda
- Cho, Judy H.
- Kong, Augustine
- Kruglyak, Leonid
- Mardis, Elaine
- Rotimi, Charles N.
- Slatkin, Montgomery
- Valle, David
- Whittemore, Alice S.
- Boehnke, Michael
- Clark, Andrew G.
- Eichler, Evan E.
- Gibson, Greg
- Haines, Jonathan L.
- Mackay, Trudy F. C.
- McCarroll, Steven A.
- Visscher, Peter M.
- Venue
- Nature
- Published
- 2009-10
- Volume
- 461
- Issue
- 7265
- Pages
- 747-753
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2831613
- OpenAlex
- W1980991473
- Cited by
- 8,336
- References
- 84
- Citations by year
- 2026: 203 · 2025: 285 · 2024: 318 · 2023: 335 · 2022: 409 · 2021: 482 · 2020: 456 · 2019: 494 · 2018: 460 · 2017: 509 · 2016: 544 · 2015: 593 · 2014: 683 · 2013: 650 · 2012: 781
- FWCI
- 58.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (5p50gm065509-10)
- National Heart, Lung, and Blood Institute (U01HL084706, R01HL072904)
- National Institute of Mental Health (R01MH084695)
- National Human Genome Research Institute (R01HG003229)
- National Institute of General Medical Sciences (P50-GM065509)
- National Center for Research Resources (UL1RR024992)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Keywords
- missing heritability, complex diseases, genetic architecture, epigenetic variation, gene-environment interaction, gene-gene interaction, polygenic risk, familial aggregation, disease prevention
- MeSH terms
- Genetics, Medical, Humans, Pedigree, Genetic Predisposition to Disease, Genetic Diseases, Inborn, Inheritance Patterns, Genome-Wide Association Study
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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