Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
Open accessAbstract
Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed approximately 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated approximately 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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?
Structural variants have been associated with autism, schizophrenia, and Crohn's disease.
“SVs have already been associated with diverse diseases, including autism2,3, schizophrenia4,5 and Crohn’s disease6,7.”
From Mapping copy number variation by population-scale genome sequencing (2011) · cites this paper as [6]
Analysis of publicly available data identified a single strong association (r2=.99) between rs10490924, a coding variant in ARMS2, and a 3′ UTR indel polymorphism associated with ARMS2 mRNA instability.
“This analysis identified a single strong association (r2=.99), between rs10490924, a coding variant in the ARMS2 gene which is the peak of association in 10q26, and a 3′ UTR indel polymorphism associated with ARMS2 mRNA instability40.”
From Seven new loci associated with age-related macular degeneration (2013) · cites this paper as [38]
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
Individual Comparisons by Ranking Methods
Wilcoxon, F. (1945) · Biometrics Bulletin · doi:10.2307/3001968 · Cited by 15,354 · see citing works
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
The Wellcome Trust Case Control Consortium, Management Committee, Burton, P. R., Clayton, D. G., Cardon, L. R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D. P., McCarthy, M. I., et al. (2007) · Nature · doi:10.1038/nature05911 · Cited by 9,442 · 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
Genetics of Food Intake Self-Regulation in Childhood: Literature Review and Research Opportunities
Faith, M. S., Carnell, S., & Kral, T. V. E. (2013) · Human Heredity · doi:10.1159/000353879 · Cited by 7,628 · see citing works
Global variation in copy number in the human genome
Redon, R., Ishikawa, S., Fitch, K. R., Feuk, L., Perry, G. H., Andrews, T. D., Fiegler, H., Shapero, M. H., Carson, A. R., Chen, W., et al. (2006) · Nature · doi:10.1038/nature05329 · Cited by 4,276 · see citing works
Strong 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 · see citing works
The Wellcome Trust Case Control Consortium, U.K.
Mossman, K. (2008) · Scientific American · doi:10.1038/scientificamerican0108-42a · Cited by 2,714 · see citing works
Evidence-based health policy—lessons from the Global Burden of Disease Study
Murray, C. J. L., & Lopez, A. D. (1996) · Science · doi:10.1126/science.274.5288.740 · Cited by 2,178 · see citing works
Origins and functional impact of copy number variation in the human genome
The Wellcome Trust Case Control Consortium, Conrad, D. F., Pinto, D., Redon, R., Feuk, L., Gokcumen, O., Zhang, Y., Aerts, J., Andrews, T. D., Barnes, C., et al. (2010) · Nature · doi:10.1038/nature08516 · Cited by 1,970 · see citing works
Prescribing Personalized Nutrition for Cardiovascular Health: Are We Ready?
Juma, S., Imrhan, V., Vijayagopal, P., & Prasad, C. (2014) · Lifestyle Genomics · doi:10.1159/000370213 · Cited by 1,905 · see citing works
Wellcome Trust Case Control Consortium, Zeggini, E., Scott, L. J., Saxena, R., Voight, B. F., Marchini, J. L., Hu, T., de Bakker, P. I., Abecasis, G. R., Almgren, P., et al. (2008) · Nature Genetics · doi:10.1038/ng.120 · Cited by 1,864 · see citing works
The Diploid Genome Sequence of an Individual Human
Levy, S., Sutton, G., Ng, P. C., Feuk, L., Halpern, A. L., Walenz, B. P., Axelrod, N., Huang, J., Kirkness, E. F., Denisov, G., et al. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050254 · Cited by 1,778 · see citing works
Large recurrent microdeletions associated with schizophrenia.
GROUP, Stefansson, H., Rujescu, D., Cichon, S., Pietiläinen, O. P. H., Ingason, A., Steinberg, S., Fossdal, R., Sigurdsson, E., Sigmundsson, T., et al. (2008) · Nature · doi:10.1038/nature07229 · Cited by 1,745 · see citing works
the GIANT Consortium (2009) · Nature Genetics · doi:10.1038/ng.287 · Cited by 1,720 · see citing works
Rare chromosomal deletions and duplications increase risk of schizophrenia
The International Schizophrenia Consortium (2008) · Nature · doi:10.1038/nature07239 · Cited by 1,475 · see citing works
Association study designs for complex diseases
Cardon, L. R., & Bell, J. I. (2001) · Nature Reviews Genetics · doi:10.1038/35052543 · Cited by 1,380 · see citing works
Copy number variation in human health, disease, and evolution
Zhang, F., Gu, W., Hurles, M. E., & Lupski, J. R. (2009) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.9.081307.164217 · Cited by 1,207 · see citing works
Mapping and sequencing of structural variation from eight human genomes
Kidd, J. M., Cooper, G. M., Donahue, W. F., Hayden, H. S., Sampas, N., Graves, T., Hansen, N., Teague, B., Alkan, C., Antonacci, F., et al. (2008) · Nature · doi:10.1038/nature06862 · Cited by 1,119 · see citing works
Mechanism and regulation of human non-homologous DNA end-joining
Lieber, M. R., Ma, Y., Pannicke, U., & Schwarz, K. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1202 · Cited by 973 · see citing works
Integrated detection and population-genetic analysis of SNPs and copy number variation
McCarroll, S. A., Kuruvilla, F. G., Korn, J. M., Cawley, S., Nemesh, J., Wysoker, A., Shapero, M. H., de Bakker, P. I. W., Maller, J. B., Kirby, A., et al. (2008) · Nature Genetics · doi:10.1038/ng.238 · Cited by 936 · see citing works
Genome architecture, rearrangements and genomic disorders
Stankiewicz, P., & Lupski, J. R. (2002) · Trends in Genetics · doi:10.1016/s0168-9525(02)02592-1 · Cited by 915 · see citing works
Lee, J. A., Carvalho, C. M. B., & Lupski, J. R. (2007) · Cell · doi:10.1016/j.cell.2007.11.037 · Cited by 914 · see citing works
A common inversion under selection in Europeans
Stefánsson, H., Helgason, A., Þorleifsson, G., Steinthórsdóttir, V., Másson, G., Barnard, J., Baker, A., Jónasdóttir, Á., Ingason, A., Gudnadottir, V. G., et al. (2005) · Nature Genetics · doi:10.1038/ng1508 · Cited by 830 · see citing works
Common deletion polymorphisms in the human genome
McCarroll, S. A., Hadnott, T. N., Perry, G. H., Sabeti, P. C., Zody, M. C., Barrett, J. C., Dallaire, S., Gabriel, S. B., Lee, C., Daly, M. J., et al. (2006) · Nature Genetics · doi:10.1038/ng1696 · Cited by 701 · see citing works
Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease
McCarroll, S. A., Huett, A., Kuballa, P., Chilewski, S. D., Landry, A., Goyette, P., Zody, M. C., Hall, J. L., Brant, S. R., Cho, J. H., et al. (2008) · Nature Genetics · doi:10.1038/ng.215 · Cited by 655 · see citing works
Psoriasis is associated with increased β-defensin genomic copy number
Hollox, E. J., Hüffmeier, U., Zeeuwen, P. L. J. M., Raquel, P., Lascorz, J., Rodijk‐Olthuis, D., van de Kerkhof, P. C. M., Traupe, H., de Jongh, G. J., den Heijer, M., et al. (2007) · Nature Genetics · doi:10.1038/ng.2007.48 · Cited by 630 · see citing works
Copy-number variation and association studies of human disease
McCarroll, S. A., & Altshuler, D. M. (2007) · Nature Genetics · doi:10.1038/ng2080 · Cited by 622 · see citing works
de Cid, R., Riveira‐Muñoz, E., Zeeuwen, P. L. J. M., Robarge, J., Liao, W. J., Dannhauser, E. N., Giardina, E., Stuart, P. E., Nair, R. P., Helms, C. A., et al. (2009) · Nature Genetics · doi:10.1038/ng.313 · Cited by 533 · see citing works
Clayton, D. G., Walker, N. M., Smyth, D. J., Pask, R., Cooper, J. D., Maier, L. M., Smink, L. J., Lam, A. C., Ovington, N. R., Stevens, H. E., et al. (2005) · Nature Genetics · doi:10.1038/ng1653 · Cited by 526 · see citing works
Fanciulli, M., Norsworthy, P. J., Petretto, E. G., Dong, R., Harper, L., Kamesh, L., Heward, J. M., Gough, S. C. L., de Smith, A. J., Blakemore, A. I. F., et al. (2007) · Nature Genetics · doi:10.1038/ng2046 · Cited by 464 · see citing works
Copy number variation at 1q21.1 associated with neuroblastoma
Diskin, S. J., Hou, C., Glessner, J., Attiyeh, E. F., Laudenslager, M., Bosse, K. R., Cole, K. A., Mossé, Y. P., Wood, A., Lynch, J. E., et al. (2009) · Nature · doi:10.1038/nature08035 · Cited by 351 · see citing works
Stankiewicz, P., & Beaudet, A. L. (2007) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2007.04.009 · Cited by 324 · see citing works
Variation analysis and gene annotation of eight MHC haplotypes: The MHC Haplotype Project
Horton, R., Gibson, R., Coggill, P. C., Miretti, M. M., Allcock, R. J. N., Almeida, J. P., Forbes, S. A., Gilbert, J. G. R., Halls, K., Harrow, J., et al. (2008) · Immunogenetics · doi:10.1007/s00251-007-0262-2 · Cited by 317 · see citing works
Locke, D. P., Sharp, A. J., McCarroll, S. A., McGrath, S. D., Newman, T. L., Cheng, Z., Schwartz, S., Albertson, D. G., Pinkel, D., Altshuler, D., et al. (2006) · The American Journal of Human Genetics · doi:10.1086/505653 · Cited by 317 · see citing works
National Cancer Institute (2020) · Definitions · doi:10.32388/f4olbl · Cited by 227 · see citing works
Progress in understanding the biology of the human mutagen LINE-1
Babushok, D. V., & Kazazian, H. H. (2007) · Human Mutation · doi:10.1002/humu.20486 · Cited by 209 · see citing works
Lieber, M. R., Yu, K., & Raghavan, S. C. (2006) · DNA repair · doi:10.1016/j.dnarep.2006.05.013 · Cited by 185 · see citing works
A robust statistical method for case-control association testing with copy number variation
Barnes, C. P., Plagnol, V., Fitzgerald, T. W., Redon, R., Marchini, J., Clayton, D. G., & Hurles, M. E. (2008) · Nature Genetics · doi:10.1038/ng.206 · Cited by 176 · see citing works
McKinney, C., Merriman, M. E., Chapman, P. T., Gow, P. J., Harrison, A. A., Highton, J., Jones, P. B. B., McLean, L., O'Donnell, J. L., Pokorny, V., et al. (2007) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2007.075028 · Cited by 160 · see citing works
Lieber, M. R., Lu, H., Gu, J., & Schwarz, K. (2007) · Cell Research · doi:10.1038/cr.2007.108 · Cited by 102 · see citing works
Mamtani, M., Rovin, B. H., Brey, R. L., Camargo, J. F., Kulkarni, H. R., Herrera, M. L., Corréa, P., Holliday, S. L., Anaya, J., & Ahuja, S. K. (2007) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2007.078048 · Cited by 94 · see citing works
Experimental aspects of copy number variant assays at CCL3L1
Field, S. F., Howson, J. M. M., Maier, L. M., Walker, S., Walker, N. M., Smyth, D. J., Armour, J. A. L., Clayton, D. G., & Todd, J. A. (2009) · Nature Medicine · doi:10.1038/nm1009-1115 · Cited by 70 · see citing works
Association of multiple sclerosis with ILT6 deficiency
Koch, S., Goedde, R., Nigmatova, V. G., Epplen, J. T., Müller, N., Seze, J. D., Vermersch, P., Momot, T., Schmidt, R. E., & Witte, T. (2005) · Genes and Immunity · doi:10.1038/sj.gene.6364187 · Cited by 51 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
A map of human genome variation from population-scale sequencing.
The 1000 Genomes Project Consortium (2010) · Nature · doi:10.1038/nature09534 · Cited by 7,877 · see citing works
An integrated map of structural variation in 2,504 human genomes
Sudmant, P. H., Rausch, T., Gardner, E. J., Handsaker, R. E., Abyzov, A., Huddleston, J., Zhang, Y., Ye, K., Jun, G., Hsi-Yang Fritz, M., et al. (2015) · Nature · doi:10.1038/nature15394 · Cited by 2,354 · see citing works
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations
O’Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., Levy, R., Ko, A., Lee, C., Smith, J. D., et al. (2012) · Nature · doi:10.1038/nature10989 · Cited by 2,165 · see citing works
Autophagy in infection, inflammation and immunity
Deretic, V., Saitoh, T., & Akira, S. (2013) · Nature Reviews Immunology · doi:10.1038/nri3532 · Cited by 1,919 · see citing works
Genome structural variation discovery and genotyping
Alkan, C., Coe, B. P., & Eichler, E. E. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2958 · Cited by 1,630 · see citing works
Missing heritability and strategies for finding the underlying causes of complex disease
Eichler, E. E., Jonathan Flint, C., Gibson, G. C., Kong, A., Leal, S. M., Moore, J. H., & Nadeau, J. H. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2809 · Cited by 1,671 · see citing works
A copy number variation morbidity map of developmental delay
Cooper, G. M., Coe, B. P., Girirajan, S., Rosenfeld, J. A., Vu, T. H., Baker, C., Williams, C., Stalker, H., Hamid, R., Hannig, V., et al. (2011) · Nature Genetics · doi:10.1038/ng.909 · Cited by 1,351 · see citing works
Mapping copy number variation by population-scale genome sequencing
1000 Genomes Project, Mills, R. E., Walter, K., Stewart, C., Handsaker, R. E., Chen, K., Alkan, C., Abyzov, A., Yoon, S. C., Ye, K., et al. (2011) · Nature · doi:10.1038/nature09708 · Cited by 1,140 · see citing works
MAGIC, Heid, I. M., Jackson, A. U., Randall, J. C., Winkler, T. W., Qi, L., Steinthorsdottir, V., Thorleifsson, G., Zillikens, M. C., Speliotes, E. K., et al. (2010) · Nature Genetics · doi:10.1038/ng.685 · Cited by 931 · see citing works
A copy number variation map of the human genome
Zarrei, M., MacDonald, J. R., Merico, D., & Scherer, S. W. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3871 · Cited by 921 · see citing works
Manning, A. K., Hivert, M., Scott, R. A., Grimsby, J., Bouatia‐Naji, N., Chen, H., Rybin, D. V., Liu, C.-T., Bielak, L. F., Prokopenko, I., et al. (2012) · Nature Genetics · doi:10.1038/ng.2274 · Cited by 805 · see citing works
Seven new loci associated with age-related macular degeneration
The AMD Gene Consortium (2013) · Nature Genetics · doi:10.1038/ng.2578 · Cited by 788 · see citing works
Epigenetic Gene Promoter Methylation at Birth Is Associated With Child’s Later Adiposity
Godfrey, K. M., Sheppard, A. M., Gluckman, P. D., Lillycrop, K. A., Burdge, G. C., McLean, C. A., Rodford, J., Slater-Jefferies, J. L., Garratt, E. S., Crozier, S., et al. (2011) · Diabetes · doi:10.2337/db10-0979 · Cited by 754 · see citing works
Diversity of Human Copy Number Variation and Multicopy Genes
Sudmant, P. H., Kitzman, J. O., Antonacci, F., Alkan, C., Malig, M., Tsalenko, A., Sampas, N., Bruhn, L., Shendure, J., 1000 Genomes Project, et al. (2010) · Science · doi:10.1126/science.1197005 · Cited by 667 · see citing works
The genetics of asthma and allergic disease: a 21st century perspective
Ober, C., & Yao, T. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01029.x · Cited by 698 · see citing works
Phenotypic impact of genomic structural variation: insights from and for human disease
Weischenfeldt, J., Symmons, O., Spitz, F., & Korbel, J. (2013) · Nature reviews genetics · doi:10.1038/nrg3373 · Cited by 646 · see citing works
Jacquemont, S., Coe, B. P., Hersch, M., Duyzend, M. H., Krumm, N., Bergmann, S., Beckmann, J. S., Rosenfeld, J. A., & Eichler, E. E. (2014) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2014.02.001 · Cited by 605 · see citing works
Genome-wide Association Study Identifies Susceptibility Loci for IgA Nephropathy
Gharavi, A., Kiryluk, K., Choi, M., Li, Y.-F., Hou, P., Xie, J.-Y., Sanna-Cherchi, S., Men, C. J., Julian, B., Wyatt, R., et al. (2011) · Nature Genetics · doi:10.1038/ng.787 · Cited by 628 · see citing works
Lepage, P., Häsler, R., Spehlmann, M. E., Rehman, A., Žvirblienė, A., Begun, A., Ott, S. J., Kupčinskas, L., Dore, J. M., Raedler, A., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.04.011 · Cited by 592 · see citing works
Discovery and Statistical Genotyping of Copy-Number Variation from Whole-Exome Sequencing Depth
Fromer, M., Moran, J. L., Chambert, K., Banks, E., Bergen, S. E., Ruderfer, D. M., Handsaker, R. E., McCarroll, S. A., O’Donovan, M. C., Owen, M. J., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.08.005 · Cited by 567 · see citing works
Todd, J. A. (2010) · Immunity · doi:10.1016/j.immuni.2010.04.001 · Cited by 560 · see citing works
The impact of structural variation on human gene expression
GTEx Consortium, Chiang, C., Scott, A. J., Davis, J. R., Tsang, E. K., Li, X., Kim, Y., Hadzic, T., Damani, F. N., Ganel, L., et al. (2017) · Nature Genetics · doi:10.1038/ng.3834 · Cited by 495 · see citing works
Progress and promise of genome-wide association studies for human complex trait genetics
Stranger, B. E., Stahl, E. A., & Raj, T. (2011) · Genetics · doi:10.1534/genetics.110.120907 · Cited by 567 · see citing works
Promise and pitfalls of the Immunochip
Cortes, A., & Brown, M. A. (2010) · Arthritis Research & Therapy · doi:10.1186/ar3204 · Cited by 479 · see citing works
Genetics of Type 2 Diabetes—Pitfalls and Possibilities
Prasad, R., & Groop, L. (2015) · Genes · doi:10.3390/genes6010087 · Cited by 458 · see citing works
Recent Insights Into the Genetics of Inflammatory Bowel Disease
Cho, J. H., & Brant, S. R. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.02.046 · Cited by 425 · see citing works
Pinto, D., Darvishi, K., Shi, X. M., Rajan, D., Rigler, D., Fitzgerald, T. W., Lionel, A. C., Thiruvahindrapuram, B., MacDonald, J. R., Mills, R. E., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1852 · Cited by 403 · see citing works
Large multiallelic copy number variations in humans
Handsaker, R. E., Doren, V. V., Berman, J. R., Genovese, G., Kashin, S., Boettger, L. M., & McCarroll, S. A. (2015) · Nature Genetics · doi:10.1038/ng.3200 · Cited by 382 · see citing works
Strawbridge, R. J., Dupuis, J., Prokopenko, I., Barker, A., Ahlqvist, E., Rybin, D., Petrie, J. R., Travers, M. E., Bouatia-Naji, N., Dimas, A. S., et al. (2011) · Diabetes · doi:10.2337/db11-0415 · Cited by 356 · see citing works
Self-citationHuman Copy Number Variation and Complex Genetic Disease
Girirajan, S., Campbell, C. D., & Eichler, E. E. (2011) · Annual Review of Genetics · doi:10.1146/annurev-genet-102209-163544 · Cited by 367 · see citing works
Mapping and characterization of structural variation in 17,795 human genomes
Genomics, N. C. F. C. D., Abel, H. J., Larson, D. E., Regier, A. A., Chiang, C., Das, I., Kanchi, K. L., Layer, R. M., Neale, B. M., Salerno, W. J., et al. (2020) · Nature · doi:10.1038/s41586-020-2371-0 · Cited by 310 · see citing works
Murea, M., Ma, L., & Freedman, B. I. (2012) · The Review of Diabetic Studies · doi:10.1900/rds.2012.9.6 · Cited by 364 · see citing works
Autophagy in immunity and cell‐autonomous defense against intracellular microbes
Deretic, V. P. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00995.x · Cited by 363 · see citing works
Genetics of Rheumatoid Arthritis — A Comprehensive Review
Kurkó, J., Besenyei, T., Laki, J., Glant, T. T., Mikecz, K., & Szekanecz, Z. (2013) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-012-8346-7 · Cited by 343 · see citing works
Relative Burden of Large CNVs on a Range of Neurodevelopmental Phenotypes
Girirajan, S., Brkanac, Z., Coe, B. P., Baker, C. A., Vives, L., Vu, T. H., Shafer, N., Bernier, R., Ferrero, G. B., Silengo, M., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002334 · Cited by 324 · see citing works
SHANK1 Deletions in Males with Autism Spectrum Disorder
Sato, D., Lionel, A. C., Leblond, C. S., Prasad, A., Pinto, D., Walker, S., O'Connor, I., Russell, C., Drmic, I. E., Hamdan, F. F., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.03.017 · Cited by 318 · see citing works
Swanson-Wagner, R. A., Eichten, S. R., Kumari, S., Tiffin, P., Stein, J. C., Ware, D., & Springer, N. M. (2010) · Genome Research · doi:10.1101/gr.109165.110 · Cited by 311 · see citing works
Contribution of Global Rare Copy-Number Variants to the Risk of Sporadic Congenital Heart Disease
Soemedi, R., Wilson, I. J., Bentham, J., Darlay, R., Töpf, A., Zelenika, D., Cosgrove, C., Setchfield, K., Thornborough, C., Granados-Riveron, J., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.08.003 · Cited by 315 · see citing works
Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis
Painter, J. N., Anderson, C. A., Nyholt, D. R., Macgregor, S., Lin, J., Lee, S. H., Lambert, A., Zhao, Z. Z., Roseman, F., Guo, Q., et al. (2011) · Nature Genetics · doi:10.1038/ng.731 · Cited by 308 · see citing works
Self-citationSheppard, S. K., Didelot, X., Méric, G., Torralbo, A., Jolley, K. A., Kelly, D. J., Bentley, S. D., Maiden, M. C. J., Parkhill, J., & Falush, D. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1305559110 · Cited by 298 · see citing works
Nik-Zainal, S., Wedge, D. C., Alexandrov, L. B., Petljak, M., Butler, A. P., Bolli, N., Davies, H. R., Knappskog, S., Martin, S., Papaemmanuil, E., et al. (2014) · Nature Genetics · doi:10.1038/ng.2955 · Cited by 277 · see citing works
Deretic, V. P. (2011) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.10.006 · Cited by 294 · see citing works
Girirajan, S., Dennis, M. Y., Baker, C. A., Malig, M., Coe, B. P., Campbell, C. D., Mark, K. M. K., Vu, T. H., Alkan, C., Cheng, Z., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.12.016 · Cited by 292 · see citing works
Programmed cell death and its role in inflammation
Yang, Y., Jiang, G., Zhang, P., & Fan, J. (2015) · Military Medical Research · doi:10.1186/s40779-015-0039-0 · Cited by 291 · see citing works
Genetics of ankylosing spondylitis—insights into pathogenesis
Brown, M. A., Kenna, T., & Wordsworth, B. P. (2015) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2015.133 · Cited by 291 · see citing works
IFN-Inducible GTPases in Host Cell Defense
Kim, B.-H., Shenoy, A. R., Kumar, P., Bradfield, C. J., & MacMicking, J. D. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.09.007 · Cited by 283 · see citing works
Ebler, J., Ebert, P., Clarke, W. E., Rausch, T., Audano, P. A., Houwaart, T., Mao, Y., Korbel, J. O., Eichler, E. E., Zody, M. C., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01043-w · Cited by 277 · see citing works
Human IRGM regulates autophagy and cell-autonomous immunity functions through mitochondria
Singh, S., Ornatowski, W., Vergne, I., Naylor, J., Delgado, M. A., Roberts, E. A., Ponpuak, M., Master, S. S., Pilli, M., White, E., et al. (2010) · Nature Cell Biology · doi:10.1038/ncb2119 · Cited by 257 · see citing works
Genome-Wide Association Studies of the Human Gut Microbiota
Davenport, E., Cusanovich, D. A., Michelini, K., Barreiro, L. B., Ober, C., & Gilad, Y. (2015) · PLoS ONE · doi:10.1371/journal.pone.0140301 · Cited by 253 · see citing works
Fakhro, K. A., Choi, M., Ware, S. M., Belmont, J. W., Towbin, J. A., Lifton, R. P., Khokha, M. K., & Brueckner, M. K. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019645108 · Cited by 251 · see citing works
Mehto, S., Jena, K. K., Nath, P., Chauhan, S., Kolapalli, S. P., Das, S. K., Sahoo, P. K., Jain, A., Taylor, G. A., & Chauhan, S. (2019) · Molecular Cell · doi:10.1016/j.molcel.2018.11.018 · Cited by 238 · see citing works
Direct Measure of the De Novo Mutation Rate in Autism and Schizophrenia Cohorts
Awadalla, P., Gauthier, J., Myers, R. A., Casals, F., Hamdan, F. F., Griffing, A. R., Côté, M., Henrion, É., Spiegelman, D., Tarabeux, J., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.07.019 · Cited by 235 · see citing works
IRGM Governs the Core Autophagy Machinery to Conduct Antimicrobial Defense
Chauhan, S., Mandell, M. A., & Deretic, V. P. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.03.020 · Cited by 231 · see citing works
High-resolution genetic mapping of maize pan-genome sequence anchors
Lü, F., Romay, M. C., Glaubitz, J. C., Bradbury, P. J., Elshire, R. J., Wang, T., Li, Y., Li, Y., Semagn, K., Zhang, X., et al. (2015) · Nature Communications · doi:10.1038/ncomms7914 · Cited by 231 · see citing works
Keshavan, M. S., Nasrallah, H. A., & Tandon, R. (2011) · Schizophrenia Research · doi:10.1016/j.schres.2011.01.011 · Cited by 227 · see citing works
Understanding type 1 diabetes through genetics: advances and prospects
Polychronakos, C., & Li, Q. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3069 · Cited by 226 · see citing works
Spencer, C. C. A., Plagnol, V., Strange, A., Gardner, M. J., Paisán‐Ruiz, C., Band, G., Barker, R., Bellenguez, C., Bhatia, K. P., Blackburn, H., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq469 · Cited by 213 · see citing works
Brown, S., Kroboth, K., Sandilands, A., Campbell, L., Pöhler, E., Kežić, S., Cordell, H. J., McLean, W. H. I., & Irvine, A. D. (2011) · Journal of Investigative Dermatology · doi:10.1038/jid.2011.342 · Cited by 211 · see citing works
Rare Deletions at the Neurexin 3 Locus in Autism Spectrum Disorder
Vaags, A. K., Lionel, A. C., Sato, D., Goodenberger, M. L., Stein, Q., Curran, S. R., Ogilvie, C. M., Ahn, J. W., Drmic, I., Senman, L., et al. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.11.025 · Cited by 209 · see citing works
Genetics of Atrial Fibrillation in 2020
Roselli, C., Rienstra, M., & Ellinor, P. T. (2020) · Circulation Research · doi:10.1161/circresaha.120.316575 · Cited by 208 · 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
Structural Variants in the Soybean Genome Localize to Clusters of Biotic Stress-Response Genes
McHale, L. K., Haun, W. J., Xu, W. W., Bhaskar, P. B., Anderson, J., Hyten, D. L., Gerhardt, D. J., Jeddeloh, J. A., & Stupar, R. M. (2012) · PLANT PHYSIOLOGY · doi:10.1104/pp.112.194605 · Cited by 203 · see citing works
Dosage sensitivity is a major determinant of human copy number variant pathogenicity
Rice, A. M., & McLysaght, A. (2017) · Nature Communications · doi:10.1038/ncomms14366 · Cited by 188 · see citing works
Kuriyama, S., Metoki, H., Kikuya, M., Obara, T., Ishikuro, M., Yamanaka, C., Nagai, M., Matsubara, H., Kobayashi, T., Sugawara, J., et al. (2019) · International Journal of Epidemiology · doi:10.1093/ije/dyz169 · Cited by 191 · see citing works
Genomics and Genetics in the Biology of Adaptation to Exercise
Bouchard, C., Rankinen, T., & Timmons, J. A. (2011) · Comprehensive physiology · doi:10.1002/cphy.c100059 · Cited by 211 · see citing works
Hor, H., Kutalik, Z., Dauvilliers, Y. A., Valsesia, A., Lammers, G. J., Donjacour, C. E. H. M., Iranzo, Á., Santamaría, J., Peraita‐Adrados, R., Vicario, J. L., et al. (2010) · Nature Genetics · doi:10.1038/ng.647 · Cited by 189 · see citing works
Watson, C. T., & Breden, F. J. (2012) · Genes and Immunity · doi:10.1038/gene.2012.12 · Cited by 175 · see citing works
Lightbody, G., Haberland, V., Browne, F., Taggart, L., Zheng, H., Parkes, E., & Blayney, J. K. (2019) · Briefings in Bioinformatics · doi:10.1093/bib/bby051 · Cited by 173 · 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
A decade of structural variants: description, history and methods to detect structural variation
Escaramís, G., Docampo, E., & Rabionet, R. (2015) · Briefings in Functional Genomics · doi:10.1093/bfgp/elv014 · Cited by 170 · see citing works
The genetics of child psychiatric disorders: focus on autism and Tourette syndrome
State, M. W. (2010) · Neuron · doi:10.1016/j.neuron.2010.10.004 · Cited by 162 · see citing works
Autophagy: A new strategy for host-directed therapy of tuberculosis
Paik, S., Kim, J. K., Chung, C., & Jo, E.-K. (2018) · Virulence · doi:10.1080/21505594.2018.1536598 · Cited by 163 · see citing works
Soemedi, R., Töpf, A., Wilson, I., Darlay, R., Rahman, T., Glen, E., Hall, D. H., Huang, N., Bentham, J., Bhattacharya, S., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr589 · Cited by 158 · see citing works
The missing link between genetic association and regulatory function
Connally, N. J., Nazeen, S., Lee, D., Shi, H., Stamatoyannopoulos, J. A., Chun, S., Cotsapas, C. J., Cassa, C. A., & Sunyaev, S. R. (2022) · eLife · doi:10.7554/elife.74970 · Cited by 144 · see citing works
Genome-wide meta-analysis for severe diabetic retinopathy
Grassi, M. A., Тихомиров, А. А., Ramalingam, S., Below, J. E., Cox, N. J., & Nicolae, D. L. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr121 · Cited by 157 · see citing works
Type 2 Diabetes Genetics: Beyond GWAS
Sanghera, D. K., & Blackett, P. R. (2012) · Journal of Diabetes & Metabolism · doi:10.4172/2155-6156.1000198 · Cited by 158 · see citing works
Genetics of diabetes – Are we missing the genes or the disease?
Groop, L., & Pociot, F. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.04.002 · Cited by 158 · see citing works
Autophagy: An Emerging Immunological Paradigm
Deretic, V. P. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1102108 · Cited by 154 · see citing works
Copy number variation in the genomes of domestic animals
Clop, A., Vidal, O., & Amills, M. (2012) · Animal Genetics · doi:10.1111/j.1365-2052.2012.02317.x · Cited by 152 · see citing works
The role of inflammasome-derived IL-1 in driving IL-17 responses
Mills, K. H. G., Dungan, L. S., Jones, S. A., & Harris, J. (2012) · Journal of Leukocyte Biology · doi:10.1189/jlb.1012543 · Cited by 153 · see citing works
McLaren, P. J., Coulonges, C., Ripke, S., van den Berg, L. H., Buchbinder, S., Carrington, M. N., Cossarizza, A., Dalmau, J., Deeks, S. G., Delaneau, O., et al. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003515 · Cited by 150 · see citing works
Naitza, S., Porcu, E., Steri, M., Taub, D. D., Mulas, A., Xiao, X., Strait, J., Dei, M., Lai, S., Busonero, F., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002480 · Cited by 148 · see citing works
Inherited genetic variation in childhood acute lymphoblastic leukemia
Moriyama, T., Relling, M. V., & Yang, J. J. J. (2015) · Blood · doi:10.1182/blood-2014-12-580001 · Cited by 149 · see citing works
Immunologic manifestations of autophagy
Deretic, V. P., Kimura, T., Timmins, G. S., Moseley, P. L., Chauhan, S., & Mandell, M. A. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73945 · Cited by 146 · see citing works
Ethnic and population differences in the genetic predisposition to human obesity
Stryjecki, C., Alyass, A., & Meyre, D. (2017) · Obesity Reviews · doi:10.1111/obr.12604 · Cited by 142 · see citing works
Thirty-five common variants for coronary artery disease: the fruits of much collaborative labour
Peden, J. F., & Farrall, M. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr384 · Cited by 142 · see citing works
The impact of human copy number variation on gene expression: Figure 1
Gamazon, E. R., & Stranger, B. E. (2015) · Briefings in Functional Genomics · doi:10.1093/bfgp/elv017 · Cited by 133 · see citing works
Structural forms of the human amylase locus and their relationships to SNPs, haplotypes and obesity
Usher, C. L., Handsaker, R. E., Esko, T., Tuke, M. A., Weedon, M. N., Hastie, A. R., Cao, H., Moon, J. E., Kashin, S., Fuchsberger, C., et al. (2015) · Nature Genetics · doi:10.1038/ng.3340 · Cited by 136 · see citing works
Recent advances in nutrition, genes and brain health
Dauncey, M. J. (2012) · Proceedings of The Nutrition Society · doi:10.1017/s0029665112000237 · Cited by 139 · see citing works
Jarick, I., Vogel, C. I. G., Scherag, S., Schäfer, H., Hebebrand, J., Hinney, A., & Scherag, A. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq518 · Cited by 136 · see citing works
Quinn, E. M., Cormican, P., Kenny, E. M., Hill, M., Anney, R., Gill, M., Corvin, A. P., & Morris, D. W. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058815 · Cited by 131 · see citing works
Dosage-sensitive genes in evolution and disease
Rice, A. M., & McLysaght, A. (2017) · BMC Biology · doi:10.1186/s12915-017-0418-y · Cited by 132 · see citing works
Carpenter, D., Dhar, S., Mitchell, L. M., Fu, B., Tyson, J., Shwan, N. A. A., Yang, F., Thomas, M., & Armour, J. A. L. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv098 · Cited by 131 · see citing works
GWAS in autoimmune thyroid disease: redefining our understanding of pathogenesis
Simmonds, M. J. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.56 · Cited by 130 · see citing works
Human inversions and their functional consequences
Puig, M., Casillas, S., Villatoro, S., & Cáceres, M. (2015) · Briefings in Functional Genomics · doi:10.1093/bfgp/elv020 · Cited by 127 · see citing works
Exploring the role of copy number variants in human adaptation
Iskow, R. C., Gökçümen, Ö., & Lee, C. (2012) · Trends in Genetics · doi:10.1016/j.tig.2012.03.002 · Cited by 128 · see citing works
Clinical interpretation of copy number variants in the human genome
Nowakowska, B. (2017) · Journal of Applied Genetics · doi:10.1007/s13353-017-0407-4 · Cited by 130 · see citing works
Understanding mutagenesis through delineation of mutational signatures in human cancer
Petljak, M., & Alexandrov, L. B. (2016) · Carcinogenesis · doi:10.1093/carcin/bgw055 · Cited by 110 · see citing works
A Lasso multi-marker mixed model for association mapping with population structure correction
Rakitsch, B., Lippert, C., Stegle, O., & Borgwardt, K. M. (2012) · Bioinformatics · doi:10.1093/bioinformatics/bts669 · Cited by 126 · see citing works
Autophagy and inflammatory diseases
Jones, S. A., Mills, K. H. G., & Harris, J. (2013) · Immunology and Cell Biology · doi:10.1038/icb.2012.82 · Cited by 125 · see citing works
- Authors
- The Wellcome Trust Case Control Consortium
- Venue
- Nature
- Published
- 2010-04
- Volume
- 464
- Issue
- 7289
- Pages
- 713-720
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2892339
- OpenAlex
- W2130542470
- Cited by
- 807
- References
- 43
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 14 · 2023: 12 · 2022: 22 · 2021: 17 · 2020: 31 · 2019: 40 · 2018: 36 · 2017: 38 · 2016: 42 · 2015: 78 · 2014: 69 · 2013: 88 · 2012: 112
- FWCI
- 69.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Lincoln Repository (University of Lincoln) (acceptedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- St George's Online Research Archive (St George's University of London) (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- PEARL (University of Plymouth) (submittedVersion, other-oa)
- HAL (submittedVersion, other-oa)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- Document Server@UHasselt (UHasselt) (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- ANU Open Research (Australian National University) (submittedVersion)
- PEARL (University of Plymouth) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- ResearchSpace (University of Auckland) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Wellcome Trust (85517, 061858, 089989, 090532, 083948)
- National Institute for Health and Care Research (NF-SI-0508-10299, NF-SI-0508-10335)
- British Heart Foundation (RG/08/014/24067, RG/09/012/28096)
- Versus Arthritis (/17552, 18475)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
- Keywords
- copy number variation, common diseases, genetic susceptibility, Crohn's disease, rheumatoid arthritis, type 1 diabetes, type 2 diabetes, IRGM, HLA, TSPAN8, false positive association, Wellcome Trust Case Control Consortium, genetic polymorphism, de novo mutations
- MeSH terms
- Arthritis, Rheumatoid, Crohn Disease, Diabetes Mellitus, Disease, Gene Frequency, Humans, Nucleic Acid Hybridization, Pilot Projects, Quality Control, Case-Control Studies, Genetic Predisposition to Disease, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Genome-Wide Association Study, DNA Copy Number Variations
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