Once and Again—Issues Surrounding Replication in Genetic Association Studies
Abstract
Over the last 15 yr, genes responsible for hundreds of inherited human diseases have been identified, enabling clinical diagnosis and the potential for therapeutic intervention. Until very recently, however, success has been limited to so-called monogenic disorders, diseases in which mutation of a single gene is both necessary and sufficient to cause disease in any given individual. Because such mutations are strictly co-inherited with disease, it is possible to use linkage analysis to identify their chromosomal location by analyzing which of a genome-wide set of markers segregates with disease in families. Genes contained within such linked regions become positional “candidates” and are next examined for mutations in affected individuals. For any such candidate gene, proof of causality typically depends on two additional lines of evidence. First, the putative causal changes should be found only in affected individuals. Second, one hopes for a “smoking gun”—that the disease-associated mutations are obviously deleterious to protein function (due to truncation or deletion of a coding region or alteration of a highly conserved residue). Success is typically declared when these criteria are all satisfied: the putative disease gene 1) is located in a chromosomal region that co-segregates with disease in affected families, 2) contains multiple independent mutations that are perfectly associated with disease status in the families, and 3) whose characteristics obviously alter protein function.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Rare nonsynonymous mutations in MC4R are found in patients with extreme early-onset obesity.
“Rare nonsynonymous mutations in MC4R are found in patients with extreme early-onset obesity (129).”
From Genetic Mapping in Human Disease (2008) · cites this paper as [129]
Cites
The Structure of Haplotype Blocks in the Human Genome
Gabriel, S. B., Schaffner, S. F., Nguyen, H., Moore, J. M., Roy, J., Blumenstiel, B., Higgins, J., DeFelice, M., Lochner, A., Faggart, M., et al. (2002) · Science · doi:10.1126/science.1069424 · Cited by 5,863 · see citing works
Self-citationThe 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 · see citing works
Targeted disruption of the melanocortin-4 receptor results in obesity in mice
Huszar, D., Lynch, C. A., Fairchild-Huntress, V., Dunmore, J. H., Fang, Q., Berkemeier, L. R., Gu, W., Kesterson, R. A., Boston, B. A., Cone, R. D., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)81865-6 · Cited by 3,030 · see citing works
A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms
The International SNP Map Working Group, Laboratories:, C. S. H., Sachidanandam, R., Weissman, D., Schmidt, S. C., Kakol, J. M., Stein, L. D., National Center for Biotechnology Information:, Marth, G., Sherry, S., et al. (2001) · Nature · doi:10.1038/35057149 · Cited by 2,977 · see citing works
Self-citationThe common PPARγ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes
Altshuler, D., Hirschhorn, J. N., Klannemark, M., Lindgren, C. M., Vohl, M.-C., Nemesh, J., Lane, C. R., Schaffner, S. F., Bolk, S., Brewer, C., et al. (2000) · Nature Genetics · doi:10.1038/79216 · Cited by 1,766 · see citing works
Self-citationA comprehensive review of genetic association studies
Hirschhorn, J. N., Lohmueller, K., Byrne, E., & Hirschhorn, K. (2002) · Genetics in Medicine · doi:10.1097/00125817-200203000-00002 · Cited by 1,674 · see citing works
Self-citationAre Rare Variants Responsible for Susceptibility to Complex Diseases?
Pritchard, J. K. (2001) · The American Journal of Human Genetics · doi:10.1086/321272 · Cited by 1,197 · see citing works
A frameshift mutation in MC4R associated with dominantly inherited human obesity
Yeo, G. S. H., Farooqi, I. S., Aminian, S., Halsall, D. J., Stanhope, R. G., & O'Rahilly, S. (1998) · Nature Genetics · doi:10.1038/2404 · Cited by 1,159 · see citing works
A frameshift mutation in human MC4R is associated with a dominant form of obesity
Vaisse, C., Clément, K., Guy-grand, B., & Froguel, P. (1998) · Nature Genetics · doi:10.1038/2407 · Cited by 1,091 · see citing works
Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity
Vaisse, C., Clement, K., Durand, E., Hercberg, S., Guy-Grand, B., & Froguel, P. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9238 · Cited by 897 · see citing works
Identification and functional analysis of novel human melanocortin-4 receptor variants.
Gu, W., Tu, Z., Kleyn, P. W., Kissebah, A. H., Duprat, L. J., Lee, J., Chin, W., Maruti, S., Deng, N., Fisher, S. L., et al. (1999) · Diabetes · doi:10.2337/diabetes.48.3.635 · Cited by 191 · see citing works
Jacobson, P., Ukkola, O. H., Rankinen, T., Snyder, E. E., Leon, A. S., Rao, D. C., Skinner, J. S., Wilmore, J. H., Lönn, L., Cowan, G. S. M., et al. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020568 · Cited by 119 · see citing works
Gotoda, T., Scott, J., & Aitman, T. J. (1997) · Diabetologia · doi:10.1007/s001250050777 · Cited by 83 · see citing works
Molecular scanning for mutations in the melanocortin‐4 receptor gene in obese/diabetic Japanese
Ohshiro, Y., Sanke, T., Ueda, K., Shimajiri, Y., Nakagawa, T., Tsunoda, K., Nishi, M., Sasaki, H., Takasu, N., & Nanjo, K. (1999) · Annals of Human Genetics · doi:10.1046/j.1469-1809.1999.6360483.x · Cited by 40 · see citing works
Molecular scanning for mutations in the melanocortin-4 receptor gene in obese/diabetic Japanese.
Ohshiro, Y., Sanke, T., Ueda, K., et al. (1999) · PubMed · doi:10.1017/s0003480099007782 · Cited by 39 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Genome-wide association studies for common diseases and complex traits
Hirschhorn, J. N., & Daly, M. J. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1521 · Cited by 2,853 · see citing works
Self-citationLohmueller, K. E., Pearce, C. L., Pike, M., Lander, E. S., & Hirschhorn, J. N. (2003) · Nature Genetics · doi:10.1038/ng1071 · Cited by 1,900 · see citing works
Self-citationGenetic Mapping in Human Disease
Altshuler, D., Daly, M. J., & Lander, E. S. (2008) · Science · doi:10.1126/science.1156409 · Cited by 1,452 · see citing works
Self-citationLarge, rare chromosomal deletions associated with severe early-onset obesity
Bochukova, E. G., Huang, N., Keogh, J., Henning, E., Purmann, C., Blaszczyk, K., Saeed, S., Hamilton-Shield, J., Clayton-Smith, J., O’Rahilly, S., et al. (2010) · Nature · doi:10.1038/nature08689 · Cited by 613 · see citing works
Kryukov, G. V., Pennacchio, L. A., & Sunyaev, S. R. (2007) · The American Journal of Human Genetics · doi:10.1086/513473 · Cited by 598 · see citing works
Gratacòs, M., González, J. R., Mercader, J. M., de Cid, R., Urretavizcaya, M., & Estivill, X. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.08.025 · Cited by 428 · see citing works
Most published research findings are false-but a little replication goes a long way.
Moonesinghe, R., Khoury, M. J., & Janssens, A. C. J. W. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040028 · Cited by 341 · see citing works
The Inherited Basis of Diabetes Mellitus: Implications for the Genetic Analysis of Complex Traits
Florez, J. C., Hirschhorn, J., & Altshuler, D. (2003) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.4.070802.110436 · Cited by 329 · see citing works
Self-citationReplication in Genome-Wide Association Studies
Kraft, P. L., Zeggini, E., & Ioannidis, J. P. A. (2009) · Statistical Science · doi:10.1214/09-sts290 · Cited by 292 · see citing works
Genetic association studies of complex traits: design and analysis issues
Newton‐Cheh, C., & Hirschhorn, J. N. (2005) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2005.01.006 · Cited by 284 · see citing works
Self-citationFan, J., Zhang, C.-S., Gu, N., Li, X.-W., Sun, W.-W., Wang, H.-Y., Feng, G.-Y., Clair, D. S., & He, L. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.10.018 · Cited by 259 · see citing works
Curses—Winner's and Otherwise—in Genetic Epidemiology
Kraft, P. (2008) · Epidemiology · doi:10.1097/ede.0b013e318181b865 · Cited by 225 · see citing works
Hinney, A., Bettecken, T., Tarnow, P., Brumm, H., Reichwald, K., Lichtner, P., Scherag, A., Nguyen, T. T., Schlumberger, P., Rief, W., et al. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2056 · Cited by 209 · see citing works
Hinney, A., Hohmann, S., Geller, F., VOGEL, C., Hess, C., Wermter, A., Brokamp, B., Goldschmidt, H., Siegfried, W., Remschmidt, H., et al. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030233 · Cited by 207 · see citing works
Zhang, C., Qi, L., Hunter, D. J., Meigs, J. B., Manson, J. E., van Dam, R. M., & Hu, F. B. (2006) · Diabetes · doi:10.2337/db06-0643 · Cited by 204 · see citing works
McCarty, C. A., Wilke, R. A., Giampietro, P. F., Wesbrook, S. D., & Caldwell, M. D. (2005) · Personalized Medicine · doi:10.1517/17410541.2.1.49 · Cited by 200 · see citing works
Attempted Replication of Reported Chronic Obstructive Pulmonary Disease Candidate Gene Associations
Hersh, C. P., DeMeo, D. L., Lange, C., Litonjua, A. A., Reilly, J. J., Kwiatkowski, D. J., Laird, N. M., Sylvia, J. S., Sparrow, D., Speizer, F. E., et al. (2005) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2005-0073oc · Cited by 188 · see citing works
Page, G. P., George, V., Go, R., Page, P. Z., & Allison, D. (2003) · American Journal of Human Genetics · doi:10.1086/378900 · Cited by 198 · see citing works
Psychiatric Disorders: Diagnosis to Therapy
Krystal, J. H., & State, M. W. (2014) · Cell · doi:10.1016/j.cell.2014.02.042 · Cited by 191 · see citing works
The role of genetic variation in the causation of mental illness: an evolution-informed framework
Uher, R. (2009) · Molecular Psychiatry · doi:10.1038/mp.2009.85 · Cited by 189 · see citing works
ENPP1/PC-1 K121Q Polymorphism and Genetic Susceptibility to Type 2 Diabetes
Abate, N. I., Chandalia, M., Satija, P., ADAMS-HUET, B. A., Grundy, S. M., Sreedharan, S., Radha, V., Deepa, R., & Mohan, V. (2005) · Diabetes · doi:10.2337/diabetes.54.4.1207 · Cited by 171 · see citing works
Power of deep, all-exon resequencing for discovery of human trait genes
Kryukov, G. V., Shpunt, A., Stamatoyannopoulos, J. A., & Sunyaev, S. R. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812824106 · Cited by 156 · see citing works
Betting Odds and Genetic Associations
Thomas, D. C., & Clayton, D. G. (2004) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djh094 · Cited by 154 · see citing works
Nath, S. K., Harley, J. B., & Lee, Y. H. (2005) · Human Genetics · doi:10.1007/s00439-005-0044-6 · Cited by 151 · see citing works
Erdmann, J., Willenborg, C., Nahrstaedt, J., Preuss, M. H., König, I. R., Baumert, J. J., Linsel‐Nitschke, P., Gieger, C., Tennstedt, S., Belcredi, P., et al. (2010) · European Heart Journal · doi:10.1093/eurheartj/ehq405 · Cited by 143 · see citing works
A large-scale candidate gene association study of age at menarche and age at natural menopause
He, C., Kraft, P., Chasman, D. I., Buring, J. E., Chen, C., Hankinson, S. E., Paré, G., Chanock, S. J., Ridker, P. M., & Hunter, D. J. (2010) · Human Genetics · doi:10.1007/s00439-010-0878-4 · Cited by 136 · see citing works
Genetic approaches to stature, pubertal timing, and other complex traits
Palmert, M. R., & Hirschhorn, J. N. (2003) · Molecular Genetics and Metabolism · doi:10.1016/s1096-7192(03)00107-0 · Cited by 135 · see citing works
Self-citationGenetics of common forms of obesity: a brief overview
Lyon, H. N., & Hirschhorn, J. N. (2005) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/82.1.215s · Cited by 132 · see citing works
Self-citationLarge quantitative effect of melanocortin-4 receptor gene mutations on body mass index
Dempfle, A., Hinney, A., Heinzel-Gutenbrunner, M., Raab, M., Geller, F., Gudermann, T., Schäfer, H., & Hebebrand, J. (2004) · Journal of Medical Genetics · doi:10.1136/jmg.2004.018614 · Cited by 132 · see citing works
Casey, B. J., Glatt, C. E., Tottenham, N., Soliman, F., Bath, K., Amso, D., Altemus, M., Pattwell, S., Jones, R., Levita, L., et al. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.03.081 · Cited by 129 · see citing works
Pussegoda, K., Ross, C. J., Visscher, H., Yazdanpanah, M., Brooks, B., Rassekh, S. R., Zada, Y. F., Dubé, M., Carleton, B., & Hayden, M. R. (2013) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2013.80 · Cited by 129 · see citing works
Fan, J., & Sklar, P. B. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001690 · Cited by 130 · see citing works
Calton, M. A., Ersoy, B. A., Zhang, S., Kane, J. P., Malloy, M. J., Pullinger, C. R., Bromberg, Y., Pennacchio, L. A., Dent, R., McPherson, R., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn431 · Cited by 127 · see citing works
Czyż, W., Morahan, J., Ebers, G., & Ramagopalan, S. (2012) · BMC Medicine · doi:10.1186/1741-7015-10-93 · Cited by 120 · see citing works
Willer, C. J., Bonnycastle, L. L., Conneely, K. N., Duren, W. L., Jackson, A., Scott, L. J., Narisu, N., Chines, P. S., Skol, A. D., Stringham, H. M., et al. (2006) · Diabetes · doi:10.2337/db06-0461 · Cited by 121 · see citing works
Genome screen for asthma and bronchial hyperresponsiveness: Interactions with passive smoke exposure
Meyers, D. A., Postma, D. S., Stine, O. C., Koppelman, G. H., Ampleford, E. J., Jongepier, H., Howard, T. D., & Bleecker, E. R. (2005) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2005.01.070 · Cited by 120 · see citing works
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 118 · see citing works
Anderson, T. J. C., Nair, S., Qin, H., Singlam, S., Brockman, A., Paiphun, L., & Nosten, F. H. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.6.2180-2188.2005 · Cited by 116 · see citing works
Qi, L., van Dam, R. M., Meigs, J. B., Manson, J. E., Hunter, D., & Hu, F. B. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl113 · Cited by 112 · see citing works
Molecular genetics of heterotaxy syndromes
Belmont, J. W., Mohapatra, B., Towbin, J. A., & Ware, S. M. (2004) · Current Opinion in Cardiology · doi:10.1097/00001573-200405000-00005 · Cited by 111 · see citing works
Determinants of the success of whole-genome association testingPreprint
Clark, A. G., Boerwinkle, E., Hixson, J. E., & Sing, C. F. (2005) · Genome Research · doi:10.1101/gr.4244005 · Cited by 111 · see citing works
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 107 · see citing works
Edwards, B. J., Haynes, C. A., Levenstien, M. A., Finch, S. J., & Gordon, D. (2005) · BMC Genetics · doi:10.1186/1471-2156-6-18 · Cited by 109 · see citing works
Required sample size and nonreplicability thresholds for heterogeneous genetic associations
Moonesinghe, R., Khoury, M. J., Liu, T., & Ioannidis, J. P. A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705554105 · Cited by 106 · see citing works
The CHRNA5–A3–B4 gene cluster in nicotine addiction
Berrettini, W. H., & Doyle, G. A. R. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.122 · Cited by 97 · see citing works
Comprehensive Testing of Positionally Cloned Asthma Genes in Two Populations
Hersh, C. P., Raby, B. A., Soto-Quirós, M. E., Murphy, A., Ávila, L., Lasky-Su, J. A., Sylvia, J. S., Klanderman, B. J., Lange, C., Weiss, S. T., et al. (2007) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200704-592oc · Cited by 93 · see citing works
Overview of the pharmacogenetics of asthma treatment
Weiss, S. T., Litonjua, A. A., Lange, C., Lazarus, R. M., Liggett, S. B., Bleecker, E. R., & Tantisira, K. G. (2006) · The Pharmacogenomics Journal · doi:10.1038/sj.tpj.6500387 · Cited by 92 · see citing works
Non-replication of association studies: “pseudo-failures” to replicate?
Gorroochurn, P., Hodge, S. E., Heiman, G. A., Durner, M., & Greenberg, D. A. (2007) · Genetics in Medicine · doi:10.1097/gim.0b013e3180676d79 · Cited by 88 · see citing works
Cho, S.-A., Park, T.-S., Yoon, D.-H., Cheong, H.-S., Namgoong, S., Park, B., Lee, H. W., Han, C., Kim, E. M., Cheong, I.-C., et al. (2008) · BMB Reports · doi:10.5483/bmbrep.2008.41.1.029 · Cited by 86 · see citing works
Hellquist, A., Zucchelli, M., Kivinen, K., Saarialho‐Kere, U., Koskenmies, S., Widén, E., Julkunen, H. A., Wong, A., Karjalainen‐Lindsberg, M., Skoog, T., et al. (2007) · Journal of Medical Genetics · doi:10.1136/jmg.2006.046185 · Cited by 85 · see citing works
Integrating epidemiology and genetic association: the challenge of gene–environment interaction
Kraft, P., & Hunter, D. (2005) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2005.1692 · Cited by 81 · see citing works
Caramori, M. L., Canani, L. H. S., Costa, L. A., & Gross, J. L. (2003) · Diabetes · doi:10.2337/diabetes.52.12.3010 · Cited by 81 · see citing works
Valli‐Jaakola, K., Lipsanen‐Nyman, M., Oksanen, L., Hollenberg, A. N., KONTULA, K. K., Bjørbæk, C., & Schalin‐Jäntti, C. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031182 · Cited by 81 · see citing works
Freedman, M. L., Pearce, C. L., Penney, K. L., Hirschhorn, J. N., Kolonel, L. N., Henderson, B. E., & Altshuler, D. (2004) · The American Journal of Human Genetics · doi:10.1086/427224 · Cited by 79 · see citing works
Self-citationCommon Variants in the ENPP1 Gene Are Not Reproducibly Associated With Diabetes or Obesity
Lyon, H. N., Florez, J. C., Bersaglieri, T., Saxena, R., Winckler, W., Almgren, P., Lindblad, U., Tuomilehto, J., Gaudet, D., Zhu, X., et al. (2006) · Diabetes · doi:10.2337/db06-0407 · Cited by 77 · see citing works
Self-citationMelanocortin-4 Receptor (MC4R) Agonists for the Treatment of Obesity
Nargund, R. P., Strack, A. M., & Fong, T. M. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm058241a · Cited by 70 · see citing works
Walsh, K. M., & Bracken, M. B. (2011) · Genetics in Medicine · doi:10.1097/gim.0b013e3182076c0c · Cited by 65 · see citing works
Clinical trials in the era of personalized oncology
Maitland, M. L., & Schilsky, R. L. (2011) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.20135 · Cited by 64 · see citing works
Thrombospondins, Their Polymorphisms, and Cardiovascular Disease
Stenina‐Adognravi, O., Topol, E. J., & Plow, E. F. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.141713 · Cited by 63 · see citing works
Replication in genetic studies of complex traits
Sillanpää, M. J., & Auranen, K. J. (2004) · Annals of Human Genetics · doi:10.1046/j.1529-8817.2004.00122.x · Cited by 59 · see citing works
Butterbach, K., Beckmann, L., de Sanjosé, S., Benavente, Y., Becker, N., Foretová, L., Maynadié, M., Cocco, P., Staines, A. S., Boffetta, P., et al. (2011) · British Journal of Haematology · doi:10.1111/j.1365-2141.2011.08632.x · Cited by 58 · see citing works
Wessel, J., Topol, E. J., Ji, M. H., Meyer, J. M., & McCarthy, J. J. (2004) · American Heart Journal · doi:10.1016/j.ahj.2003.12.013 · Cited by 58 · see citing works
Finding unique filter sets in PLATO: a precursor to efficient interaction analysis in GWAS data.
Grady, B. J., Torstenson, E. S., DUDEK, S. M., Giles, J., Sexton, D., & Ritchie, M. D. (2010) · PubMed · Cited by 55 · see citing works
Zee, R. Y. L., Cook, N. R., Cheng, S., ERLICH, H. A., Lindpaintner, K., & Ridker, P. M. (2006) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2006.01754.x · Cited by 55 · see citing works
Genetic associations with reflexive visual attention in infancy and childhood
Lundwall, R. A., Dannemiller, J. L., & Goldsmith, H. H. (2015) · Developmental Science · doi:10.1111/desc.12371 · Cited by 54 · see citing works
Mechanisms of Disease: genetic insights into the etiology of type 2 diabetes and obesity
Lindgren, C. M., & McCarthy, M. I. (2008) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0723 · Cited by 55 · see citing works
Functional genomics of membrane transporters in human populationsPreprint
Urban, T. J., Sebro, R., Hurowitz, E. H., Leabman, M. K., Badagnani, I., Lagpacan, L. L., RISCH, N. J., & Giacomini, K. M. (2005) · Genome Research · doi:10.1101/gr.4356206 · Cited by 53 · see citing works
Complex and multi-allelic copy number variation in human disease
Usher, C. L., & McCarroll, S. A. (2015) · Briefings in Functional Genomics · doi:10.1093/bfgp/elv028 · Cited by 53 · see citing works
Association Studies of BMI and Type 2 Diabetes in the Neuropeptide Y Pathway
Campbell, C. D., Lyon, H. N., Nemesh, J. C., Drake, J. A., Tuomilehto, J., Gaudet, D., Zhu, X., Cooper, R., Ardlie, K., Groop, L., et al. (2007) · Diabetes · doi:10.2337/db06-1051 · Cited by 52 · see citing works
Self-citationLack of Support for the Association between GAD2 Polymorphisms and Severe Human Obesity
Swarbrick, M. M., Waldenmaier, B., Pennacchio, L. A., Lind, D. L., Cavazos, M. M., Geller, F., Merriman, R. B., Ustaszewska, A., Malloy, M. J., Scherag, A., et al. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030315 · Cited by 51 · see citing works
Pharmacogenetics and Pharmacogenomics in Oncology Therapeutic Antibody Development
Li, Y., & Beckman, R. A. (2005) · BioTechniques · doi:10.2144/000112043 · Cited by 50 · see citing works
A Conservative Meta-Analysis of Linkage and Linkage-Association Studies of Developmental Dyslexia
Grigorenko, E. L. (2005) · Scientific Studies of Reading · doi:10.1207/s1532799xssr0903_6 · Cited by 50 · see citing works
Chasing genes in Alzheimer?s and Parkinson?s disease
Bertoli‐Avella, A. M., Oostra, B. A., & Heutink, P. (2004) · Human Genetics · doi:10.1007/s00439-004-1097-7 · Cited by 48 · see citing works
Defining the genetic profile of endometriosis (Review)
Vassilopoulou, L., Matalliotakis, M., Zervou, M. I., Matalliotaki, C., Krithinakis, K., Matalliotakis, I., Spandidos, D. A., & Goulielmos, G. N. (2019) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2019.7346 · Cited by 49 · see citing works
Tavares, V., Hirata, R. D. C., Rodrigues, A. C., Monte, O., Salles, J. E. N., Scalissi, N. M., Speranza, A. C., & Hirata, M. H. (2004) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2004.00453.x · Cited by 45 · see citing works
Reporting of Human Genome Epidemiology (HuGE) association studies: An empirical assessment
Yesupriya, A., Εvangelou, Ε., Kavvoura, F. K., Patsopoulos, N. A., Clyne, M., Walsh, M. C., Lin, B. K., Yu, W., GWINN, M. L., Ioannidis, J. P. A., et al. (2008) · BMC Medical Research Methodology · doi:10.1186/1471-2288-8-31 · Cited by 44 · see citing works
MEF2A sequence variants and coronary artery disease: a change of heart?
Altshuler, D., & Hirschhorn, J. N. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200524715 · Cited by 41 · see citing works
Self-citationAsthma Steroid Pharmacogenetics: A Study Strategy to Identify Replicated Treatment Responses
Weiss, S. T., Lake, S. L., Silverman, E. S., Silverman, E. K., Richter, B., Drazen, J. M., & Tantisira, K. G. (2004) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200409-043ms · Cited by 41 · see citing works
Bayesian approach to discovering pathogenic SNPs in conserved protein domains
Cai, Z., Tsung, E. F., Marinescu, V. D., Ramoni, M. F., Riva, A., & Kohane, I. S. (2004) · Human Mutation · doi:10.1002/humu.20063 · Cited by 40 · see citing works
de Oliveira, D. S. B., da Silva, R. A. B., de Oliveira, S. A. S., Dutra, A. L. T., dos Santos, A. S., Praxedes, A. D. N., Belém, L. C., Antunes, L. A. A., Lips, A., Nelson‐Filho, P., et al. (2018) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2018.04.010 · Cited by 39 · see citing works
National Emphysema Treatment Trial State of the Art: Genetics of Emphysema
Hersh, C. P., DeMeo, D. L., & Silverman, E. K. (2008) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200706-078et · Cited by 39 · see citing works
Failure to replicate an association of SNPs in the oxidized LDL receptor gene (OLR1) with CAD
Knowles, J. W., Assimes, T. L., Boerwinkle, E., Fortmann, S. P., Go, A. S., Grove, M. L., Hlatky, M. A., Iribarren, C., Li, J. Z., Myers, R., et al. (2008) · BMC Medical Genetics · doi:10.1186/1471-2350-9-23 · Cited by 38 · see citing works
Mutation analysis of the MCHR1 gene in human obesity
Wermter, A., Reichwald, K., Büch, T., Geller, F., Platzer, C., Huse, K., Hess, C., Remschmidt, H., Gudermann, T. W., Preibisch, G., et al. (2005) · European Journal of Endocrinology · doi:10.1530/eje.1.01917 · Cited by 37 · see citing works
Genetic susceptibility to sporadic ovarian cancer: A systematic review
Braem, M. G. M., Schouten, L. J., Peeters, P. H. M., van den Brandt, P. A., & Onland‐Moret, N. C. (2011) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2011.05.002 · Cited by 36 · see citing works
Thavamanikumar, S., McManus, L. J., Ades, P. K., Bossinger, G., Stackpole, D. J., Kerr, R. J., Hadjigol, S., Freeman, J. S., Vaillancourt, R. E., Zhu, P. X., et al. (2014) · Tree Genetics & Genomes · doi:10.1007/s11295-014-0787-0 · Cited by 35 · see citing works
Genetic Determinants of Prepubertal and Pubertal Growth and Development
Thomis, M. A., & Towne, B. (2006) · Food and Nutrition Bulletin · doi:10.1177/15648265060274s509 · Cited by 33 · see citing works
Ganna, A., Lee, D., Ingelsson, E., & Yudi Pawitan, Y. (2014) · Briefings in Bioinformatics · doi:10.1093/bib/bbu033 · Cited by 32 · see citing works
Gu, D., Ge, D., Snieder, H., He, J., Chen, S., Huang, J., Li, B., Chen, R., & Qiang, B. (2006) · Journal of Hypertension · doi:10.1097/01.hjh.0000226194.21311.2f · Cited by 29 · see citing works
Pharmacogenetics, Race, and Psychiatry: Prospects and Challenges
Jones, D. S., & Perlis, R. H. (2006) · Harvard Review of Psychiatry · doi:10.1080/10673220600642895 · Cited by 29 · see citing works
Pharmacogenetic Studies of Antidepressant Response: How Far from the Clinic?
Perlis, R. H. (2007) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2006.12.004 · Cited by 28 · see citing works
Emerging trends in the search for genetic variants predisposing to human obesity
Swarbrick, M. M., & Vaisse, C. (2003) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/01.mco.0000078997.96795.03 · Cited by 28 · see citing works
The Growth Hormone Receptor in Growth
Bougneres, P. F., & Goffin, V. (2007) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2006.08.003 · Cited by 27 · see citing works
Gouni‐Berthold, I., Giannakidou, E., Müller‐Wieland, D., Faust, M., Kotzka, J., Berthold, H. K., & Krone, W. (2005) · Journal of Hypertension · doi:10.1097/00004872-200502000-00012 · Cited by 27 · see citing works
Role of Genetic Susceptibility in Nicotine Addiction and Chronic Obstructive Pulmonary Disease
Pérez-Rubio, G., Córdoba-Lanús, E., Cupertino, P., Cartujano‐Barrera, F., Campos, M., & Falfán‐Valencia, R. (2019) · Revista de investigaci�n Cl�nica · doi:10.24875/ric.18002617 · Cited by 26 · see citing works
van den Berg, F. F., Kempeneers, M. A., van Santvoort, H. C., Zwinderman, A. H., Issa, Y., & Boermeester, M. A. (2019) · BJS Open · doi:10.1002/bjs5.50231 · Cited by 27 · see citing works
Improving rigor and reproducibility in nonhuman primate research
Bliss‐Moreau, E., Amara, R. R., Buffalo, E. A., Colman, R. J., Embers, M. E., Morrison, J. H., Quillen, E. E., Sacha, J. B., & Roberts, C. T. (2021) · American Journal of Primatology · doi:10.1002/ajp.23331 · Cited by 22 · see citing works
Kardia, S. L. R., Greene, M., Boerwinkle, E., Turner, S. T., & Kullo, I. (2008) · BMC Medical Genomics · doi:10.1186/1755-8794-1-16 · Cited by 33 · see citing works
MERTK polymorphisms associated with risk of haematological disorders among Korean SLE patients
Cheong, H. S., Lee, S. O., Choi, C., Sung, Y., Shin, H. D., & Bae, S. (2006) · Lara D. Veeken · doi:10.1093/rheumatology/kel182 · Cited by 24 · see citing works
Cui, J., Randell, E. W., Renouf, J., Sun, G., Green, R., Han, F.-Y., & Xie, Y. (2006) · American Heart Journal · doi:10.1016/j.ahj.2006.06.002 · Cited by 24 · see citing works
Case-Control Genetic Association Studies in Gastrointestinal Disease: Review and Recommendations
Saito, Y. A., Talley, N. J., de Andrade, M., & Petersen, G. M. (2006) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2006.00587.x · Cited by 24 · see citing works
- Authors
- Hirschhorn, J. N., & Altshuler, D.
- Affiliations
- Boston Children's Hospital (US)
- Harvard University (US)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2002-10
- Volume
- 87
- Issue
- 10
- Pages
- 4438-4441
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2071348149
- Cited by
- 181
- References
- 14
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 5 · 2014: 5 · 2013: 6 · 2012: 6
- FWCI
- 9.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- genetic association studies, replication, monogenic disorders, linkage analysis, candidate genes, pathogenic variants, protein function
- MeSH terms
- Chromosome Mapping, Humans, Genetic Linkage, Mutation, Obesity, Proteins, Receptors, Corticotropin, Chromosome Segregation, Genetic Diseases, Inborn, Receptor, Melanocortin, Type 4
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
