The DOI matches its Crossref record; 84 of the 84 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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
Flagged first, then by citations
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
Cited by
Sorted by citations
Items 801–900 of 1,079
Cohort Profile: The International Childhood Cardiovascular Cohort (i3C) Consortium
Dwyer, T., Sun, C., Magnussen, C. G., Raitakari, O. T., Schork, N. J., Venn, A., Burns, T. L., Juonala, M., Steinberger, J., Sinaiko, A. R., et al. (2012) · International Journal of Epidemiology · doi:10.1093/ije/dys004 · Cited by 120
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 132
Impact of limited population diversity of genome-wide association studies
Haga, S. B. (2010) · Genetics in Medicine · doi:10.1097/gim.0b013e3181ca2bbf · Cited by 117
The immunogenetics of primary biliary cirrhosis: A comprehensive review
Webb, G. J., Siminovitch, K. A., & Hirschfield, G. M. (2015) · Journal of Autoimmunity · doi:10.1016/j.jaut.2015.07.004 · Cited by 118
Genome‐wide Association Study of Autism Spectrum Disorder in the East Asian Populations
Liu, X., Shimada, T., Otowa, T., Wu, Y., Kawamura, Y., Tochigi, M., Iwata, Y., Umekage, T., Toyota, T., Maekawa, M., et al. (2015) · Autism Research · doi:10.1002/aur.1536 · Cited by 118
Contributions of the d-serine pathway to schizophrenia
Labrie, V., Wong, A. H. C., & Roder, J. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.01.030 · Cited by 121
Next Generation Sequencing of Pooled Samples: Guideline for Variants’ Filtering
Anand, S. K., Mangano, E., Barizzone, N., Bordoni, R., Sorosina, M., Clarelli, F., Corrado, L., Boneschi, F. M., D’Alfonso, S., & Bellis, G. D. (2016) · Scientific Reports · doi:10.1038/srep33735 · Cited by 117
Gene-by-environment interactions in urban populations modulate risk phenotypes
Favé, M.-J., Lamaze, F. C., Soave, D. M., Hodgkinson, A., Gauvin, H., Bruat, V., Grenier, J., Gbeha, E., Skead, K., Smargiassi, A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03202-2 · Cited by 125
Nested epistasis enhancer networks for robust genome regulation
Lin, X., Liu, Y., Liu, S., Zhu, X., Wu, L., Zhu, Y., Zhao, D., Xu, X., Chemparathy, A., Wang, H., et al. (2022) · Science · doi:10.1126/science.abk3512 · Cited by 112
Siontis, K. C. M., Patsopoulos, N. A., & Ioannidis, J. P. A. (2010) · European Journal of Human Genetics · doi:10.1038/ejhg.2010.26 · Cited by 117
Genomics and anterior segment dysgenesis: a review
Itō, Y., & Walter, M. A. (2013) · Clinical and Experimental Ophthalmology · doi:10.1111/ceo.12152 · Cited by 119
Zila, C. T., Samayoa, L. F., Santiago, R., Butrón, A., & Holland, J. B. (2013) · G3 Genes Genomes Genetics · doi:10.1534/g3.113.007328 · Cited by 117
The genetic basis of Gilles de la Tourette Syndrome
Paschou, P. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.01.016 · Cited by 119
Genetics of impulsive behaviour
Bevilacqua, L. M., & Goldman, D. A. (2013) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2012.0380 · Cited by 129
Zhou, L., Brouwers, N., Benilova, I., Vandersteen, A., Mercken, M. H., Laere, K. V., Damme, P. V., Demedts, D., LEUVEN, F. V., Sleegers, K., et al. (2011) · EMBO Molecular Medicine · doi:10.1002/emmm.201100138 · Cited by 122
Quantitative Genetics of Food Intake in Drosophila melanogaster
Garlapow, M. E., Huang, W., Yarboro, M. T., Peterson, K. R., & Mackay, T. F. C. (2015) · PLoS ONE · doi:10.1371/journal.pone.0138129 · Cited by 114
Self-citationShen, C., Gao, J., Sheng, Y., Dou, J., Zhou, F., Zheng, X., Ko, R., Tang, X., Zhu, C., Yin, X., et al. (2016) · Frontiers in Genetics · doi:10.3389/fgene.2016.00003 · Cited by 120
Beyond genomics: understanding exposotypes through metabolomics
Rattray, N. J. W., Deziel, N. C., Wallach, J. D., Khan, S. A., Vasiliou, V., Ioannidis, J. P. A., & Johnson, C. H. (2018) · Human Genomics · doi:10.1186/s40246-018-0134-x · Cited by 121
Genetic Susceptibility to Chronic Kidney Disease – Some More Pieces for the Heritability Puzzle
Cañadas‐Garre, M., Anderson, K., Cappa, R., Skelly, R., Smyth, L. J., McKnight, A. J., & Maxwell, A. P. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00453 · Cited by 116
Detecting Rare Variant Associations by Identity-by-Descent Mapping in Case-Control Studies
Browning, S. R., & Thompson, E. A. (2012) · Genetics · doi:10.1534/genetics.111.136937 · Cited by 116
Taneera, J., Fadista, J., Ahlqvist, E., Atac, D., Ottosson-Laakso, E., Wollheim, C. B., & Groop, L. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu610 · Cited by 119
Asthma Genetics in the Post-GWAS Era
Ober, C. (2016) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201507-459mg · Cited by 121
Genetics: Implications for Prevention and Management of Coronary Artery Disease
Assimes, T. L., & Roberts, R. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2016.10.039 · Cited by 118
van Steenwyk, G., Roszkowski, M., Manuella, F., Franklin, T. B., & Mansuy, I. M. (2018) · Environmental Epigenetics · doi:10.1093/eep/dvy023 · Cited by 116
Into the Wild: GWAS Exploration of Non-coding RNAs
Giral, H., Landmesser, U., & Kratzer, A. (2018) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2018.00181 · Cited by 113
Xu, L., Cole, J. B., Bickhart, D. M., Hou, Y., Song, J., VanRaden, P. M., Sonstegard, T. S., Tassell, C. P. V., & Liu, G. E. (2014) · BMC Genomics · doi:10.1186/1471-2164-15-683 · Cited by 117
Bookman, E., McAllister, K. A., Gillanders, E. M., Wanke, K. L., Balshaw, D. M., Rutter, J. L., Reedy, J., Shaughnessy, D. P., Agurs‐Collins, T., Paltoo, D. N., et al. (2011) · Genetic Epidemiology · doi:10.1002/gepi.20571 · Cited by 119
Self-citationVery Early-onset Inflammatory Bowel Disease
Moran, C. J., Klein, C., Muise, A. M., & Snapper, S. B. (2015) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000329 · Cited by 115
Bohacek, J., Farinelli, M., Mirante, O., Steiner, G., Gapp, K., Coiret, G., Ebeling, M., Durán-Pacheco, G., Iniguez, A. L., Manuella, F., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.80 · Cited by 111
What is complex about complex disorders?
Mitchell, K. J. (2012) · Genome biology · doi:10.1186/gb-2012-13-1-237 · Cited by 126
Boosting the Power of Schizophrenia Genetics by Leveraging New Statistical Tools
Andreassen, O. A., Thompson, W. K., & Dale, A. M. (2013) · Schizophrenia Bulletin · doi:10.1093/schbul/sbt168 · Cited by 112
Meta‐analysis of sex‐specific genome‐wide association studies
Mägi, R., Lindgren, C. M., & Morris, A. P. (2010) · Genetic Epidemiology · doi:10.1002/gepi.20540 · Cited by 110
Anderson, C. A., Soranzo, N., Zeggini, E., & Barrett, J. C. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1000580 · Cited by 114
Polygenic risk scores for schizophrenia and bipolar disorder associate with addiction
Reginsson, G. W., Ingason, A., Euesden, J., Bjornsdottir, G., Olafsson, S., Sigurdsson, E., Oskarsson, H., Tyrfingsson, T., Runarsdottir, V., Hansdottir, I., et al. (2018) · Addiction Biology · doi:10.1111/adb.12496 · Cited by 112
The Current and Future Use of Ridge Regression for Prediction in Quantitative Genetics
de Vlaming, R., & Groenen, P. J. F. (2015) · BioMed Research International · doi:10.1155/2015/143712 · Cited by 117
The effects of social origins and cognitive ability on educational attainment
Bukodi, E., Erikson, R. S., & Goldthorpe, J. H. (2014) · Acta Sociologica · doi:10.1177/0001699314543803 · Cited by 125
Regions of homozygosity and their impact on complex diseases and traits
Ku, C., Naidoo, N., Teo, S. M., & Yudi Pawitan, Y. (2010) · Human Genetics · doi:10.1007/s00439-010-0920-6 · Cited by 114
Vanholme, B., Cesarino, I., Goeminne, G., Kim, H., Marroni, F., Acker, R. V., Vanholme, R., Morreel, K., Ivens, B., Pinosio, S., et al. (2013) · New Phytologist · doi:10.1111/nph.12179 · Cited by 114
Human genome diversity: frequently asked questions
Barbujani, G., & Colonna, V. (2010) · Trends in Genetics · doi:10.1016/j.tig.2010.04.002 · Cited by 117
Genomics of elite sporting performance: what little we know and necessary advances
Pitsiladis, Y. P., Wang, G., Wolfarth, B., Scott, R. A., Fuku, N., Miyamoto‐Mikami, E., He, Z., Fiuza‐Luces, C., Eynon, N., & Lucía, A. (2013) · British Journal of Sports Medicine · doi:10.1136/bjsports-2013-092400 · Cited by 117
Leveraging gene-environment interactions and endotypes for asthma gene discovery
Bønnelykke, K., & Ober, C. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.01.006 · Cited by 113
Statistical methods for genome-wide association studies
Wang, M. H., Cordell, H. J., & Steen, K. V. (2018) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2018.04.008 · Cited by 126
Liu, R., Gōng, J., Xiāo, X., Zhang, Z., Lǐ, J., Liú, À., Lú, Q., Shāng, H., Shí, Y., Gě, Q., et al. (2018) · Frontiers in Plant Science · doi:10.3389/fpls.2018.01067 · Cited by 119
Clinical application of next-generation sequencing to the practice of neurology
Rexach, J. E., Lee, H., Martínez-Agosto, J. A., Nemeth, A. H., & Fogel, B. L. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30033-x · Cited by 117
Grotzinger, A. D., de la Fuente, J., Privé, F., Nivard, M. G., & Tucker–Drob, E. M. (2021) · Biological Psychiatry · doi:10.1016/j.biopsych.2022.05.029 · Cited by 103
Human genetics and genomics a decade after the release of the draft sequence of the human genome
Naidoo, N., Yudi Pawitan, Y., Soong, R., Cooper, D. N., & Ku, C. (2011) · Human Genomics · doi:10.1186/1479-7364-5-6-577 · Cited by 117
Epigenomics reveals a functional genome anatomy and a new approach to common disease
Feinberg, A. P. (2010) · Nature Biotechnology · doi:10.1038/nbt1010-1049 · Cited by 115
Genetic architecture of cancer and other complex diseases: lessons learned and future directions
Hindorff, L. A., Gillanders, E. M., & Manolio, T. A. (2011) · Carcinogenesis · doi:10.1093/carcin/bgr056 · Cited by 115
Self-citationThe Genetic Architecture of Schizophrenia: New Mutations and Emerging Paradigms
Rodriguez‐Murillo, L., Gogos, J. A., & Karayiorgou, M. (2011) · Annual Review of Medicine · doi:10.1146/annurev-med-072010-091100 · Cited by 121
Genome-wide association study of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Europe
Génin, E., Schumacher, M. C., Roujeau, J., Naldi, L., Liß, Y., Kazma, R., Sekula, P., Hovnanian, A., & Mockenhaupt, M. (2011) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-6-52 · Cited by 113
jMorp: Japanese Multi Omics Reference Panel
Tadaka, S., Saigusa, D., Motoike, I. N., Inoue, J., Aoki, Y., Shirota, M., Koshiba, S., Yamamoto, M. P., & Kinoshita, K. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx978 · Cited by 110
Regulatory variants: from detection to predicting impact
Rojano, E., Seoane, P., Ranea, J. A. G., & Perkins, J. R. (2018) · Briefings in Bioinformatics · doi:10.1093/bib/bby039 · Cited by 120
Maugeri, A., Barchitta, M., Mazzone, M. G., Giuliano, F., Basile, G., & Agodi, A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19072118 · Cited by 119
The Multifaceted Role of Epoxide Hydrolases in Human Health and Disease
Gautheron, J., & Jéru, I. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010013 · Cited by 111
Evolution of polygenic traits under global vs local adaptation
Yeaman, S. (2022) · Genetics · doi:10.1093/genetics/iyab134 · Cited by 114
Modelling the Effects of Penetrance and Family Size on Rates of Sporadic and Familial Disease
Al‐Chalabi, A., & Lewis, C. M. (2011) · Human Heredity · doi:10.1159/000330167 · Cited by 118
Neutral theory for life histories and individual variability in fitness components
Steiner, U. K., & Tuljapurkar, S. D. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1018096109 · Cited by 113
Phenotypes of childhood asthma: are they real?
Spycher, B. D., Silverman, M. A., & Kuehni, C. E. (2010) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2010.03541.x · Cited by 113
Hochstenbach, R., Buizer‐Voskamp, J. E., Vorstman, J. A. S., & Ophoff, R. A. (2011) · Cytogenetic and Genome Research · doi:10.1159/000332928 · Cited by 114
Comparison of Family History and SNPs for Predicting Risk of Complex Disease
Do, C. B., Hinds, D. A., Francke, U., & Eriksson, N. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002973 · Cited by 118
Genome-wide association studies in cancer--current and future directions
Chung, C. C., Magalhães, W. C. S., Bosquet, J. G., & Chanock, S. J. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp273 · Cited by 110
FastEpistasis: a high performance computing solution for quantitative trait epistasis
Schuepbach, T., Xénarios, I., Bergmann, S., & Kapur, K. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq147 · Cited by 110
Genetics of neurodegenerative diseases: an overview
Pihlstrøm, L., Wiethoff, S., & Houlden, H. (2017) · Handbook of clinical neurology · doi:10.1016/b978-0-12-802395-2.00022-5 · Cited by 120
Basha, M. H., Demeer, B., Revençu, N., Helaers, R., Theys, S., Saba, S. B., Boute, O., Devauchelle, B., François, G., Bayet, B., et al. (2018) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2017-105110 · Cited by 112
Myopia: is the nature‐nurture debate finally over?
Morgan, I. G., & Rose, K. A. (2018) · Clinical and Experimental Optometry · doi:10.1111/cxo.12845 · Cited by 117
Bernshtein, B., Curato, C., Ιωάννου, Μ., Thaiss, C. A., Gross-Vered, M., Kolesnikov, M., Wang, Q., David, E., Chappell‐Maor, L., Harmelin, A., et al. (2019) · Science Immunology · doi:10.1126/sciimmunol.aau6571 · Cited by 116
Chambers, J. C., Abbott, J., Zhang, W., Turro, E., Scott, W. R., Tan, S.-T., Afzal, U., Afaq, S., Loh, M. C. S., Lehne, B. C., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0102645 · Cited by 113
Self-citationGrain protein content variation and its association analysis in barley
Cai, S., Yu, G., Chen, X., Huang, Y., Jiang, X., Zhang, G., & Jin, X. (2013) · BMC Plant Biology · doi:10.1186/1471-2229-13-35 · Cited by 111
The overdue promise of short tandem repeat variation for heritability
Press, M. O., Carlson, K. D., & Queitsch, C. (2014) · Trends in Genetics · doi:10.1016/j.tig.2014.07.008 · Cited by 114
Evidence of Inbreeding Depression on Human Height
McQuillan, R., Eklund, N., Pirastu, N., Kuningas, M., McEvoy, B. P., Esko, T., Corre, T., Davies, G., Kaakinen, M., Lyytikäinen, L., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002655 · Cited by 112
Self-citationGene–Gene and Gene–Environment Interactions in Apolipoprotein L1 Gene-Associated Nephropathy
Freedman, B. I., & Skorecki, K. L. (2014) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.01330214 · Cited by 109
Bridging the genotype–phenotype gap: what does it take?
Gjuvsland, A. B., Vik, J. O., Beard, D. A., Hunter, P. J., & Omholt, S. W. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2012.248864 · Cited by 115
Sehgal, D., Autrique, E., Singh, R. P., Ellis, M., Singh, S., & Dreisigacker, S. (2017) · Scientific Reports · doi:10.1038/srep41578 · Cited by 110
Toxoplasmosis: A pathway to neuropsychiatric disorders
Tyebji, S., Seizova, S., Hannan, A. J., & Tonkin, C. J. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.11.012 · Cited by 112
On the concepts and measures of diversity in the genomics era
Kanaka, K. K., Sukhija, N., Goli, R. C., Singh, S., Ganguly, I., Dixit, S. P., Dash, A., & Malik, A. A. (2023) · Current Plant Biology · doi:10.1016/j.cpb.2023.100278 · Cited by 130
Ultrafast genome-wide scan for SNP–SNP interactions in common complex diseasePreprint
Prabhu, S., & Pe’er, I. (2012) · Genome Research · doi:10.1101/gr.137885.112 · Cited by 110
Using GWAS to identify genetic predisposition in hepatic autoimmunity
Webb, G. J., & Hirschfield, G. M. (2016) · Journal of Autoimmunity · doi:10.1016/j.jaut.2015.08.016 · Cited by 108
Disease-association analysis of an inflammation-related feedback loop
Murakami, M., Harada, M., Kamimura, D., Ogura, H., Okuyama, Y., Kumai, N., Okuyama, A., Singh, R., Jiang, J.-J., Atsumi, T., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.01.028 · Cited by 110
“Although positional cloning based on SNP analysis and genome-wide exome deep-sequencing studies have identified rare disease-causing mutations in several genes as the single most important risk factor for various complex diseases and disorders, recent GWAS analyses have identified numerous putatively susceptible loci…”
BackgroundAvramopoulos, D., Pearce, B. D., McGrath, J. A., Wolyniec, P. S., Wang, R., Eckart, N., Hatzimanolis, A., Goes, F. S., Nestadt, G., Mullé, J. G., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0116696 · Cited by 115
Lubomirov, R., di Iulio, J., Fayet, A., Colombo, S. F., Martínez, R., Marzolini, C., Furrer, H., Vernazza, P., Calmy, A., Cavassini, M. L., et al. (2010) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e328336eee4 · Cited by 116
Genome-wide gene and pathway analysis
Luo, L., Peng, G., Zhu, Y., Dong, H., Amos, C. I., & Xiong, M. (2010) · European Journal of Human Genetics · doi:10.1038/ejhg.2010.62 · Cited by 112
Development and Application of High-density SNP Arrays in Genomic Studies of Domestic Animals
Fan, B., Du, Z., Gorbach, D. M., & Rothschild, M. F. (2010) · Asian-Australasian Journal of Animal Sciences · doi:10.5713/ajas.2010.r.03 · Cited by 111
Gene‐Environment Interactions in Cancer Epidemiology: A National Cancer Institute Think Tank Report
Hutter, C. M., Mechanic, L. E., Chatterjee, N., Kraft, P. L., & Gillanders, E. M. (2013) · Genetic Epidemiology · doi:10.1002/gepi.21756 · Cited by 110
Desch, K. C., Ozel, A. B., Siemieniak, D. R., Kalish, Y., Shavit, J. A., Thornburg, C. D., Sharathkumar, A. A., McHugh, C., Laurie, C. C., Crenshaw, A., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219885110 · Cited by 107
Maternal diet as a modifier of offspring epigenetics
Lillycrop, K. A., & Burdge, G. C. (2015) · Journal of Developmental Origins of Health and Disease · doi:10.1017/s2040174415000124 · Cited by 113
The genetics of familial combined hyperlipidaemia
Brouwers, M. C. G. J., van Greevenbroek, M. M. J., Stehouwer, C. D. A., de Graaf, J., & Stalenhoef, A. F. H. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.15 · Cited by 109
Dynamic Role of trans Regulation of Gene Expression in Relation to Complex Traits
Yao, C., Joehanes, R., Johnson, A. D., Huan, T., Liu, C., Freedman, J. E., Munson, P. J., Hill, D. E., Vidal, M., & Levy, D. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.02.003 · Cited by 106
Vosberg, D., Leyton, M., & Flores, C. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0561-7 · Cited by 106
Significance testing in ridge regression for genetic data
Cule, E., Vineis, P., & Iorio, M. D. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-372 · Cited by 116
Drug discovery for autism spectrum disorder: challenges and opportunities
Ghosh, A., Michalon, A., Lindemann, L., Fontoura, P., & Santarelli, L. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4102 · Cited by 108
Patterns of genomic changes with crop domestication and breeding
Shi, J., & Lai, J. (2015) · Current Opinion in Plant Biology · doi:10.1016/j.pbi.2015.01.008 · Cited by 109
Epigenetic mechanisms in migraine: a promising avenue?
Eising, E., Datson, N. A., van den Maagdenberg, A. M. J. M., & Ferrari, M. D. (2013) · BMC Medicine · doi:10.1186/1741-7015-11-26 · Cited by 112
A century after Fisher: time for a new paradigm in quantitative genetics
Nelson, R. M., Pettersson, M. E., & Carlborg, Ö. (2013) · Trends in Genetics · doi:10.1016/j.tig.2013.09.006 · Cited by 116
Strategic Approaches to Unraveling Genetic Causes of Cardiovascular Diseases
Marian, A. J., & Belmont, J. W. (2011) · Circulation Research · doi:10.1161/circresaha.110.236067 · Cited by 109
Patel, C. J., Chen, R., Kodama, K., Ioannidis, J. P. A., & Butte, A. J. (2013) · Human Genetics · doi:10.1007/s00439-012-1258-z · Cited by 110
A random forest approach to capture genetic effects in the presence of population structure
Stephan, J., Stegle, O., & Beyer, A. (2015) · Nature Communications · doi:10.1038/ncomms8432 · Cited by 115
Muñoz, M., Pong‐Wong, R., Canela‐Xandri, O., Rawlik, K., Haley, C., & Tenesa, A. (2016) · Nature Genetics · doi:10.1038/ng.3618 · Cited by 106
The Developmental Origins of Health and Disease (DOHaD) Concept
Gluckman, P. D., Buklijaš, T., & Hanson, M. A. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-801383-0.00001-3 · Cited by 130
Morgan, I. G., He, M., & Rose, K. A. (2016) · Retina · doi:10.1097/iae.0000000000001272 · Cited by 108
Brown, A. A., Viñuela, A., Delaneau, O., Spector, T. D., Small, K. S., & Dermitzakis, E. T. (2017) · Nature Genetics · doi:10.1038/ng.3979 · Cited by 102
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.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
