Genomewide Association Studies and Human Disease
Open accessAbstract
Genomewide association studies have uncovered many genetic variants that confer susceptibility to disease. This article describes the genomewide association study and new approaches that may address some of its limitations.
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
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 identification of common, complex disease genes, such as those contributing to type 2 diabetes, coronary artery disease, and hypertension has largely relied on population-based approaches (e.g. GWAS) rather than family-based studies.
“Unlike Mendelian diseases, the identification of common, complex disease genes, such as those contributing to type 2 diabetes, coronary artery disease, and hypertension has largely relied on population-based approaches ( e.g. genome wide association studies or GWAS) rather than family-based studies.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A genome-wide association study identifies novel risk loci for type 2 diabetes
Sladek, R., Rocheleau, G., Rung, J., Dina, C., Shen, L., Serre, D., Boutin, P., Vincent, D., Belisle, A., Hadjadj, S., et al. (2007) · Nature · doi:10.1038/nature05616 · Cited by 2,993 · see citing works
A HapMap harvest of insights into the genetics of common disease
Manolio, T. A., Brooks, L. D., & Collins, F. S. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34772 · Cited by 889 · see citing works
A survey of genetic human cortical gene expression
Myers, A. J., Gibbs, J. R., Webster, J. A., Rohrer, K., Zhao, A., Marlowe, L., Kaleem, M., Leung, D., Bryden, L., Nath, P., et al. (2007) · Nature Genetics · doi:10.1038/ng.2007.16 · Cited by 479 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 39
- [1]Hunter DJ Kraft P Drinking from the fire hose — statistical issues in genome-wide association studies N Engl J Med 2007 357 436 439 17634446
- [2]International HapMap Consortium A haplomap type of the human genome Nature 2005 437 1299 1320 16255080 PMC1880871
- [3]Wang WY Barratt BJ Clayton DG Todd JA Genome-wide association studies: theoretical and practical concerns Nat Rev Genet 2005 6 109 118 15716907
- [5]Lupski JR Structural variation in the human genome N Engl J Med 2007 356 1169 1171 17360997
- [6]Singleton AB Farrer M Johnson J α-Synuclein locus triplication causes Parkinson’s disease Science 2003 302 841 14593171
- [7]Sebat J Lakshmi B Malhotra D Strong association of de novo copy number mutations with autism Science 2007 316 445 449 17363630 PMC2993504
- [8]Need AC Ge D Weale ME A genome-wide investigation of SNPs and CNVs in schizophrenia PLoS Genet 2009 5 2 e1000373. PMC2631150 19197363
- [9]Kraft P Hunter DJ Genetic risk prediction — are we there yet? N Engl J Med 2009 360 1701 1703 19369656
- [10]Goldstein DB Common genetic variation and human traits N Engl J Med 2009 360 1696 1698 19369660
- [11]Hirschhorn JN Genomewide association studies — illuminating biologic pathways N Engl J Med 2009 360 1699 1701 19369661
- [12]Lander ES Linton LM Birren B Initial sequencing and analysis of the human genome Nature 2001 409 860 921 [Erratum, Nature 2001;412:565.] 11237011
- [13]Venter JC Adams MD Myers EW The sequence of the human genome Science 2001 291 1304 1351 [Erratum, Science 2001;292:1838.] 11181995
- [14]Su AI Cooke MP Ching KA Large-scale analysis of the human and mouse transcriptomes Proc Natl Acad Sci U S A 2002 99 4465 4470 11904358 PMC123671
- [16]Margulies M Egholm M Altman WE Genome sequencing in microfabricated high-density picolitre reactors Nature 2005 437 376 380 16056220 PMC1464427
- [17]Brenner S Johnson M Bridgham J Gene expression analysis by massively parallel signature sequencing (MPSS) on microbead arrays Nat Biotechnol 2000 18 630 634 [Erratum, Nat Technol 2000;18:1021.] 10835600
- [18]Olson M Enrichment of super-sized resequencing targets from the human genome Nat Methods 2007 4 891 892 17971778
- [19]Wheeler DA Srinivasan M Egholm M The complete genome of an individual by massively parallel DNA sequencing Nature 2008 452 872 876 18421352
- [22]Terwilliger JD Hiekkalinna T An utter refutation of the “Fundamental Theorem of the HapMap.” Eur J Hum Genet 2006 14 426 437 16479260
- [23]Risch N Merikangas K The future of genetic studies of complex human diseases Science 1996 273 1516 1517 8801636
- [24]Hardy J Singleton A The future of genetic analysis of neurological disorders Neurobiol Dis 2000 7 65 69 10783291
- [25]Kennedy GC German MS Rutter WJ The minisatellite in the diabetes susceptibility locus IDDM2 regulates insulin transcription Nat Genet 1995 9 293 298 7773292
- [26]Cheung VG Spielman RS Ewens KG Weber TM Morley M Burdick JT Mapping determinants of human gene expression by regional and genome-wide association Nature 2005 437 1365 1369 16251966 PMC3005311
- [27]Moffatt MF Kabesch M Liang L Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma Nature 2007 448 470 473 17611496
- [28]Emilsson V Thorleifsson G Zhang B Genetics of gene expression and its effect on disease Nature 2008 452 423 428 18344981
- [30]Bouzigon E Corda E Aschard H Effect of 17q21 variants and smoking in early-onset asthma N Engl J Med 2008 359 1985 1993 18923164
- [31]Melquist S Craig DW Huentelman MJ Identification of a novel risk locus for progressive supranuclear palsy by a pooled genomewide scan of 500,288 single-nucleotide polymorphisms Am J Hum Genet 2007 80 769 778 17357082 PMC1852701
- [32]Myers AJ Pittman AM Zhao AS The MAPT H1c risk haplotype is associated with increased expression of tau and especially of 4 repeat containing transcripts Neurobiol Dis 2007 25 561 570 17174556
- [33]Sethupathy P Collins FS MicroRNA target site polymorphisms and human disease Trends Genet 2008 24 489 497 18778868
- [34]Ng PC Levy S Huang J Genetic variation in an individual human exome PLoS Genet 2008 4 8 e1000160. PMC2493042 18704161
- [35]Cohen JC Kiss RS Pertsemlidis A Marcel YL McPherson R Hobbs HH Multiple rare alleles contribute to low plasma levels of HDL cholesterol Science 2004 305 869 872 15297675
- [36]Goldstein JL Brown MS Molecular medicine: the cholesterol quartet Science 2001 292 1310 1312 11360986
- [37]Clark IE Dodson MW Jiang C Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin Nature 2006 441 1162 1166 16672981
- [38]Park J Lee SB Lee S Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin Nature 2006 441 1157 1161 16672980
- [39]Polymeropoulos MH Lavedan C Leroy E Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease Science 1997 276 2045 2047 9197268
- [40]Farrer M Maraganore DM Lockhart P α-Synuclein gene haplotypes are associated with Parkinson’s disease Hum Mol Genet 2001 10 1847 1851 11532993
- [41]Klein RJ Zeiss C Chew EY Complement factor H polymorphism in age-related macular degeneration Science 2005 308 385 389 15761122 PMC1512523
- [42]Haines JL Hauser MA Schmidt S Complement factor H variant increases the risk of age-related macular degeneration Science 2005 308 419 421 15761120
- [43]Edwards AO Ritter R Abel KJ Manning A Panhuysen C Farrer LA Complement factor H polymorphism and age-related macular degeneration Science 2005 308 421 424 15761121
- [44]Li M Atmaca-Sonmez P Othman M CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degeneration Nat Genet 2006 38 1049 1054 16936733 PMC1941700
Cited by
Sorted by citations
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., et al. (2015) · Genetics in Medicine · doi:10.1038/gim.2015.30 · Cited by 32,594 · see citing works
“genome wide association studies or GWAS) rather than family-based studies.(50,51) Currently, numerous GWAS reports have resulted in the cataloguing of over 1200 risk alleles for common, complex diseases and traits.”
BackgroundFinding 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
Biological, clinical and population relevance of 95 loci for blood lipids
Teslovich, T. M., Musunuru, K., Smith, A. V., Edmondson, A. C., Stylianou, I. M., Koseki, M., Pirruccello, J. P., Ripatti, S., Chasman, D. I., Willer, C. J., et al. (2010) · Nature · doi:10.1038/nature09270 · Cited by 3,527 · see citing works
A high-coverage genome sequence from an archaic denisovan individual
Meyer, M., Kircher, M., Gansauge, M.-T., Li, H., Racimo, F., Mallick, S., Schraiber, J. G., Jay, F., Prüfer, K., de Filippo, C., et al. (2012) · Science · doi:10.1126/science.1224344 · Cited by 1,967 · see citing works
Genomewide Association Studies and Assessment of the Risk of Disease
Manolio, T. A. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0905980 · Cited by 1,512 · see citing works
Gilman, S. R., Iossifov, I., Levy, D., Ronemus, M., Wigler, M., & Vitkup, D. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.021 · Cited by 701 · see citing works
Genetic variability in the regulation of gene expression in ten regions of the human brain
UK Brain Expression Consortium, Ramasamy, A., North American Brain Expression Consortium, Trabzuni, D., Guelfi, S., Varghese, V., Smith, C., Walker, R., De, T., Coin, L., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3801 · Cited by 644 · see citing works
Self-citationHan, B., & Eskin, E. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.04.014 · Cited by 680 · see citing works
Tobacco-smoking-related differential DNA methylation: 27K discovery and replication
Breitling, L. P., Yang, R., Korn, B., Burwinkel, B., & Brenner, H. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.03.003 · Cited by 640 · see citing works
The X chromosome and immune associated genes
Bianchi, I., Lleo, A., Gershwin, M. E., & Invernizzi, P. (2012) · Journal of Autoimmunity · doi:10.1016/j.jaut.2011.11.012 · Cited by 378 · see citing works
Clusterin in Alzheimer’s Disease: Mechanisms, Genetics, and Lessons From Other Pathologies
Foster, E. M., Dangla-Valls, A., Lovestone, S., Ribe, E. M., & Buckley, N. J. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00164 · Cited by 381 · see citing works
Genetics of Human Social Behavior
Ebstein, R. P., Israel, S., Chew, S. H., Zhong, S., & Knafo, A. (2010) · Neuron · doi:10.1016/j.neuron.2010.02.020 · Cited by 323 · see citing works
The Psychiatric GWAS Consortium: Big Science Comes to Psychiatry
Sullivan, P. F. (2010) · Neuron · doi:10.1016/j.neuron.2010.10.003 · Cited by 285 · see citing works
Control of fetal hemoglobin: new insights emerging from genomics and clinical implications
Thein, S. L., Menzel, S., Lathrop, M., & Garner, C. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp401 · Cited by 250 · see citing works
Alzheimer's Disease Mechanisms and Emerging Roads to Novel Therapeutics
Sala Frigerio, C., & De Strooper, B. (2016) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-070815-014015 · Cited by 116 · see citing works
Systems genetics analysis of gene-by-environment interactions in human cells
Romanoski, C. E., Lee, S., Kim, M. J., Ingram-Drake, L., Plaisier, C. L., Yordanova, R., Tilford, C., Guan, B., He, A., Gargalovic, P. S., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.02.002 · Cited by 111 · see citing works
New Insights into Monogenic Causes of Osteoporosis
Mäkitie, R. E., Costantini, A., Kämpe, A., Alm, J. J., & Mäkitie, O. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00070 · Cited by 108 · see citing works
A demonstration of conservation genomics for threatened species management
Wright, B. R., Farquharson, K. A., McLennan, E. A., Belov, K., Hogg, C. J., & Grueber, C. E. (2020) · Molecular Ecology Resources · doi:10.1111/1755-0998.13211 · Cited by 69 · see citing works
Synthetic associations in the context of genome-wide association scan signals
Orozco, G., Barrett, J. C., & Zeggini, E. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq368 · Cited by 61 · see citing works
Smallwood, T. L., Gatti, D. M., Quizon, P., Weinstock, G. M., Jung, K.-C., Zhao, L., Hua, K., Pomp, D., & Bennett, B. J. (2014) · G3 Genes|Genomes|Genetics · doi:10.1534/g3.114.014704 · Cited by 54 · see citing works
Genomic Analysis of Left Ventricular Remodeling
Sarwar, R., & Cook, S. A. (2009) · Circulation · doi:10.1161/circulationaha.108.797225 · Cited by 13 · see citing works
- Authors
- Hardy, J., & Singleton, A.
- Affiliations
- UCL Queen Square Institute of Neurology (GB)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2009-04-23
- Volume
- 360
- Issue
- 17
- Pages
- 1759-1768
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC3422859
- OpenAlex
- W2138020005
- Cited by
- 733
- References
- 3
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 9 · 2023: 10 · 2022: 22 · 2021: 18 · 2020: 20 · 2019: 23 · 2018: 27 · 2017: 24 · 2016: 36 · 2015: 36 · 2014: 58 · 2013: 71 · 2012: 90
- FWCI
- 71.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DigitalGeorgetown (Georgetown University Library) (submittedVersion)
- Funders
- Parkinson's UK (G-0907)
- National Institutes of Health (Z01-AG000949)
- 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 › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- genome-wide association study, genetic susceptibility, genetic variants, human disease, genetic epidemiology
- MeSH terms
- Disease, Environment, Humans, Mutation, Genetic Variation, Gene Expression, Genetic Predisposition to Disease, 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