Adjusting for Heritable Covariates Can Bias Effect Estimates in Genome-Wide Association Studies
Open accessAbstract
In recent years, a number of large-scale genome-wide association studies have been published for human traits adjusted for other correlated traits with a genetic basis. In most studies, the motivation for such an adjustment is to discover genetic variants associated with the primary outcome independently of the correlated trait. In this report, we contend that this objective is fulfilled when the tested variants have no effect on the covariate or when the correlation between the covariate and the outcome is fully explained by a direct effect of the covariate on the outcome. For all other scenarios, an unintended bias is introduced with respect to the primary outcome as a result of the adjustment, and this bias might lead to false positives. Here, we illustrate this point by providing examples from published genome-wide association studies, including large meta-analysis of waist-to-hip ratio and waist circumference adjusted for body mass index (BMI), where genetic effects might be biased as a result of adjustment for body mass index. Using both theory and simulations, we explore this phenomenon in detail and discuss the ramifications for future genome-wide association studies of correlated traits and diseases.
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Disease modifying therapy was not included as it is not a confounder and may instead introduce collider bias.
“Disease modifying therapy was not included as it is not a confounder (i.e. does not influence genotype) and may instead introduce collider bias57.”
From Locus for severity implicates CNS resilience in progression of multiple sclerosis (2023) · cites this paper as [57]
Conditioned GWAS from mtCOJO are free of collider biases when estimating causal relationships between depression and each comorbid condition.
“Conditioned GWAS generated from mtCOJO are free of collider biases when estimate causal relationship between depression and each comorbid condition.49”
From Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions (2021) · cites this paper as [49]
Adjustment of waist-hip ratio variants for body mass index is likely to have biased the effect of genome-wide variants associated with unadjusted waist-hip ratio away from the null.
“This adjustment is likely to have biased the effect of genome-wide variants associated with unadjusted WHR (away from the null).”
From Commentary: Two-sample Mendelian randomization: opportunities and challenges (2016) · cites this paper as [17]
Cites
Principal components analysis corrects for stratification in genome-wide association studies
Price, A. L., Patterson, N. J., Plenge, R. M., Weinblatt, M. E., Shadick, N. A., & Reich, D. (2006) · Nature Genetics · doi:10.1038/ng1847 · Cited by 10,248 · see citing works
Self-citationAn integrated map of genetic variation from 1,092 human genomes
The 1000 Genomes Project Consortium (2012) · Nature · doi:10.1038/nature11632 · Cited by 7,711 · see citing works
Causal Diagrams for Epidemiologic Research
Greenland, S., Pearl, J., & Robins, J. M. (1999) · Epidemiology · doi:10.1097/00001648-199901000-00008 · Cited by 3,728 · see citing works
Air Pollution and Hospital Admissions for Heart Disease in Eight U.S. Counties
Schwartz, J. D. (1999) · Epidemiology · doi:10.1097/00001648-199901000-00005 · Cited by 3,044 · see citing works
Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs
Cross-Disorder Group of the Psychiatric Genomics Consortium (2013) · Nature Genetics · doi:10.1038/ng.2711 · Cited by 2,263 · see citing works
Overadjustment bias and unnecessary adjustment in epidemiologic studies.
Schisterman, E. F., Cole, S. R., & Platt, R. W. (2009) · Epidemiology · doi:10.1097/ede.0b013e3181a819a1 · Cited by 2,096 · cited 1× · see citing works
“Here, classical epidemiologists advise against adjustment for C, since C is in the causal pathway and hence not a confounder.(12,13) In contrast, instances can be found where genetic epidemiologists seek the controlled direct causal effect of G on Y by noting their intent to identify variants associated with the outco…”
BackgroundMaternal Pesticide Exposure from Multiple Sources and Selected Congenital Anomalies
Shaw, G. M., Wasserman, C. R., O’Malley, C. D., Nelson, V. E., & Jackson, R. J. (1999) · Epidemiology · doi:10.1097/00001648-199901000-00011 · Cited by 1,783 · see citing works
Hernan, M. A. (2002) · American Journal of Epidemiology · doi:10.1093/aje/155.2.176 · Cited by 1,445 · see citing works
Thorleifsson, G., Walters, G. B., Gudbjartsson, D. F., Steinthorsdottir, V., Sulem, P., Helgadottir, A., Styrkarsdottir, U., Gretarsdottir, S., Thorlacius, S., Jonsdottir, I., et al. (2009) · Nature Genetics · doi:10.1038/ng.274 · Cited by 1,375 · see citing works
Understanding mechanisms underlying human gene expression variation with RNA sequencing
Pickrell, J. K., Marioni, J. C., Pai, A. A., Degner, J. F., Engelhardt, B. E., Nkadori, E., Veyrieras, J.-B., Stephens, M., Gilad, Y., & Pritchard, J. K. (2010) · Nature · doi:10.1038/nature08872 · Cited by 1,256 · 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
Self-citationEfficient multivariate linear mixed model algorithms for genome-wide association studies
Zhou, X., & Stephens, M. (2014) · Nature Methods · doi:10.1038/nmeth.2848 · Cited by 841 · see citing works
Scott, R. A., Lagou, V., Welch, R., Wheeler, E., Montasser, M. E., Luan, J., Mägi, R., Strawbridge, R. J., Rehnberg, E., Gustafsson, S., et al. (2012) · Nature Genetics · doi:10.1038/ng.2385 · Cited by 817 · 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 806 · see citing works
Insulin Biosynthesis: Evidence for a Precursor
Steiner, D. F., Cunningham, D. D., Spigelman, L., & Aten, B. (1967) · Science · doi:10.1126/science.157.3789.697 · Cited by 713 · see citing works
Hancock, D. B., Eijgelsheim, M., Wilk, J. B., Gharib, S. A., Loehr, L. R., Marciante, K. D., Franceschini, N., van Durme, Y. M. T. A., Chen, T.-H., Barr, R. G., et al. (2009) · Nature Genetics · doi:10.1038/ng.500 · Cited by 633 · see citing works
Pervasive Sharing of Genetic Effects in Autoimmune Disease
Cotsapas, C., Voight, B. F., Rossin, E., Lage, K., Neale, B. M., Wallace, C., Abecasis, G. R., Barrett, J. C., Behrens, T., Cho, J., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002254 · Cited by 606 · see citing works
Fallibility in estimating direct effects
Cole, S. R., & Hernán, M. A. (2002) · International Journal of Epidemiology · doi:10.1093/ije/31.1.163 · Cited by 548 · see citing works
Abundant Pleiotropy in Human Complex Diseases and Traits
Sivakumaran, S., Agakov, F. V., Τheodoratou, E., Prendergast, J. G. D., Zgaga, L., Manolio, T. A., Rudan, I., McKeigue, P., Wilson, J. F., & Campbell, H. J. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.10.004 · Cited by 534 · see citing works
Andreassen, O. A., Djurovic, S., Thompson, W. K., Schork, A. J., Kendler, K. S., O’Donovan, M. C., Rujescu, D., Werge, T., van de Bunt, M., Morris, A. P., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.01.001 · Cited by 506 · see citing works
Juul, A., Dalgaard, P., Blum, W. F., Bang, P., Hall, K. E., Michaelsen, K. F., Müller, J., & Skakkebæk, N. E. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.8.7543116 · Cited by 463 · see citing works
Korte, A., Vilhjálmsson, B. J., Segura, V., Platt, A., Long, Q., & Nordborg, M. (2012) · Nature Genetics · doi:10.1038/ng.2376 · Cited by 440 · see citing works
Self-citationChan, J. M. (2002) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/94.14.1099 · Cited by 433 · see citing works
Randall, J. C., Winkler, T. W., Kutalik, Z., Berndt, S. I., Jackson, A. U., Monda, K. L., Kilpeläinen, T. O., Esko, T., Mägi, R., Li, S., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003500 · Cited by 409 · see citing works
Heritability of Left Ventricular Mass
Post, W. S., Larson, M. G., Myers, R. H., Galderisi, M., & Levy, D. A. (1997) · Hypertension · doi:10.1161/01.hyp.30.5.1025 · Cited by 216 · see citing works
Aschard, H., Vilhjálmsson, B. J., Greliche, N., Morange, P., Trégouët, D., & Kraft, P. (2014) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2014.03.016 · Cited by 188 · see citing works
Self-citationHigh heritability of metabolomic profiles in families burdened with premature cardiovascular disease
Shah, S. H., Hauser, E. R., Bain, J. R., Muehlbauer, M. J., Haynes, C. S., Stevens, R. D., Wenner, B. R., Dowdy, Z. E., Granger, C. B., Ginsburg, G. S., et al. (2009) · Molecular Systems Biology · doi:10.1038/msb.2009.11 · Cited by 147 · see citing works
Genome-wide association analysis identifies six new loci associated with forced vital capacity
Loth, D. W., Artigas, M. S., Gharib, S. A., Wain, L. V., Franceschini, N., Koch, B., Pottinger, T. D., Smith, A. V., Duan, Q., Oldmeadow, C. J., et al. (2014) · Nature Genetics · doi:10.1038/ng.3011 · Cited by 138 · see citing works
Mills, G. W., Lévy, J., Sampson, M., Walker, M., Avery, P. J., Hitman, G. A., Hattersley, A. T., & McCarthy, M. I. (2004) · Diabetologia · doi:10.1007/s00125-004-1338-2 · Cited by 129 · see citing works
Pirinen, M., Donnelly, P., & Spencer, C. C. A. (2013) · The Annals of Applied Statistics · doi:10.1214/12-aoas586 · Cited by 99 · see citing works
Stergiakouli, E., Gaillard, R., Tavaré, J. M., Balthasar, N., Loos, R. J., Taal, H. R., Evans, D. M., Rivadeneira, F., St Pourcain, B., Uitterlinden, A. G., et al. (2014) · Obesity · doi:10.1002/oby.20840 · Cited by 90 · see citing works
Informed Conditioning on Clinical Covariates Increases Power in Case-Control Association Studies
Zaitlen, N., Lindström, S., Paşaniuc, B., Cornelis, M. C., Genovese, G., Pollack, S. J., Barton, A. C., Bickeböller, H., Bowden, D. W., Eyre, S., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1003032 · Cited by 86 · see citing works
Self-citationCausal inference from indirect experiments
Pearl, J. (1995) · Artificial Intelligence in Medicine · doi:10.1016/0933-3657(95)00027-3 · Cited by 76 · see citing works
Heritability of the Ankle-Brachial Index
Murabito, J. M., Guo, C., Fox, C. S., & D’Agostino, R. B. (2006) · American Journal of Epidemiology · doi:10.1093/aje/kwj295 · Cited by 75 · see citing works
A genome-wide association study identifies novel loci associated with circulating IGF-I and IGFBP-3
Kaplan, R. C., Petersen, A.-K., Chen, M., Teumer, A., Glazer, N. L., Döring, A., Lam, C. S. P., Friedrich, N., Newman, A. B., Müller‐Nurasyid, M., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddq560 · Cited by 67 · see citing works
Heritability Analysis of Cytokines as Intermediate Phenotypes of Tuberculosis
Stein, C. M., Guwatudde, D., Nakakeeto, M., Peters, P., Elston, R. C., Tiwari, H. K., Mugerwa, R. D., & Whalen, C. C. (2003) · The Journal of Infectious Diseases · doi:10.1086/375249 · Cited by 62 · see citing works
Mefford, J., & Witte, J. S. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1003096 · Cited by 60 · see citing works
Vansteelandt, S., Goetgeluk, S., Lutz, S. M., Waldman, I. D., Lyon, H. N., Schadt, E. E., Weiss, S. T., & Lange, C. (2009) · Genetic Epidemiology · doi:10.1002/gepi.20393 · Cited by 52 · see citing works
Flagged first, then by citations
2 of the 40 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
An atlas of genetic correlations across human diseases and traits
ReproGen Consortium, Bulik-Sullivan, B., Psychiatric Genomics Consortium, Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control Consortium 3, Finucane, H. K., Anttila, V., Gusev, A., Day, F. R., Loh, P.-R., Duncan, L., et al. (2015) · Nature Genetics · doi:10.1038/ng.3406 · Cited by 4,255 · see citing works
Self-citationCausal associations between risk factors and common diseases inferred from GWAS summary data
Zhu, Z., Zheng, Z., Zhang, F., Wu, Y., Trzaskowski, M., Maier, R., Robinson, M. R., McGrath, J. J., Visscher, P. M., Wray, N. R., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02317-2 · Cited by 951 · see citing works
The genetic architecture of the human cerebral cortex
Grasby, K. L., Jahanshad, N., Painter, J. N., Colodro-Conde, L., Bralten, J., Hibar, D. P., Lind, P. A., Pizzagalli, F., Ching, C. R. K., McMahon, M. A. B., et al. (2020) · Science · doi:10.1126/science.aay6690 · Cited by 876 · see citing works
Commentary: Two-sample Mendelian randomization: opportunities and challenges
Lawlor, D. A. (2016) · International Journal of Epidemiology · doi:10.1093/ije/dyw127 · Cited by 810 · see citing works
The trans-ancestral genomic architecture of glycemic traits
Chen, J., Spracklen, C. N., Marenne, G., Varshney, A., Corbin, L. J., Luan, J., Willems, S. M., Wu, Y., Zhang, X., Horikoshi, M., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00852-9 · Cited by 798 · see citing works
Mendelian randomization in cardiometabolic disease: challenges in evaluating causality
Holmes, M. V., Ala-Korpela, M., & Smith, G. D. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.78 · Cited by 679 · see citing works
Sex-dependent dominance at a single locus maintains variation in age at maturity in salmon
Barson, N. J., Aykanat, T., Hindar, K., Baranski, M., Bolstad, G. H., Fiske, P., Jacq, C., Jensen, A. J., Johnston, S. E., Karlsson, S., et al. (2015) · Nature · doi:10.1038/nature16062 · Cited by 627 · see citing works
Lotta, L. A., Gulati, P., Day, F. R., Payne, F., Ongen, H., van de Bunt, M., Gaulton, K. J., Eicher, J. D., Sharp, S. J., Luan, J., et al. (2016) · Nature Genetics · doi:10.1038/ng.3714 · Cited by 587 · see citing works
Schizophrenia Working Group of the Psychiatric Genomics Consortium, Loh, P.-R., Bhatia, G., Gusev, A., Finucane, H. K., Bulik-Sullivan, B. K., Pollack, S. J., de Candia, T. R., Lee, S. H., Wray, N. R., et al. (2015) · Nature Genetics · doi:10.1038/ng.3431 · Cited by 449 · see citing works
Self-citationGenome-wide associations for birth weight and correlations with adult disease
Horikoshi, M., Beaumont, R. N., Day, F. R., Warrington, N. M., Kooijman, M. N., Fernandez-Tajes, J. J., Feenstra, B., van Zuydam, N. R., Gaulton, K. J., Grarup, N., et al. (2016) · Nature · doi:10.1038/nature19806 · Cited by 495 · see citing works
Levey, D. F., Stein, M. B., Wendt, F. R., Pathak, G. A., Zhou, H., Aslan, M., Quaden, R., Harrington, K. M., Nuñez, Y. Z., Overstreet, C., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00860-2 · Cited by 422 · see citing works
Ligthart, S., Vaez, A., Võsa, U., Stathopoulou, M. G., de Vries, P. S., Prins, B. P., van der Most, P. J., Tanaka, T., Naderi, E., Rose, L. M., et al. (2018) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2018.09.009 · Cited by 416 · see citing works
Klimentidis, Y. C., Raichlen, D. A., Bea, J., Garcia, D. O., Wineinger, N. E., Mandarino, L. J., Alexander, G. E., Chen, Z., & Going, S. B. (2018) · International Journal of Obesity · doi:10.1038/s41366-018-0120-3 · Cited by 403 · see citing works
Distinguishing genetic correlation from causation across 52 diseases and complex traits
O’Connor, L. J., & Price, A. L. (2018) · Nature Genetics · doi:10.1038/s41588-018-0255-0 · Cited by 394 · see citing works
Self-citationDale, C. E., Fatemifar, G., Palmer, T. M., White, J., Prieto-Merino, D., Zabaneh, D., Engmann, J. E. L., Shah, T., Wong, A., Warren, H. R., et al. (2017) · Circulation · doi:10.1161/circulationaha.116.026560 · Cited by 345 · see citing works
Zhu, Z., Guo, Y., Shi, H., Liu, C.-L., Panganiban, R. A. M., Chung, W., O’Connor, L. J., Himes, B. E., Gazal, S., Hasegawa, K., et al. (2019) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2019.09.035 · Cited by 344 · see citing works
Local Genetic Correlation Gives Insights into the Shared Genetic Architecture of Complex Traits
Shi, H., Mancuso, N., Spendlove, S. J., & Paşaniuc, B. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.09.022 · Cited by 345 · see citing works
Principles and methods for transferring polygenic risk scores across global populations
Kachuri, L., Chatterjee, N., Hirbo, J. B., Schaid, D. J., Martin, I. K., Kullo, I. J., Kenny, E. E., Paşaniuc, B., Auer, P. L., Conomos, M. P., et al. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-023-00637-2 · Cited by 338 · see citing works
Lotta, L. A., Wittemans, L. B. L., Zuber, V., Stewart, I. D., Sharp, S. J., Luan, J., Day, F. R., Li, C., Bowker, N., Cai, L., et al. (2018) · JAMA · doi:10.1001/jama.2018.19329 · Cited by 229 · see citing works
Locus for severity implicates CNS resilience in progression of multiple sclerosis
International Multiple Sclerosis Genetics Consortium, Harroud, A., Stridh, P., McCauley, J. L., Saarela, J., van den Bosch, A. M. R., Engelenburg, H. J., Beecham, A. H., Alfredsson, L., Alikhani, K., et al. (2023) · Nature · doi:10.1038/s41586-023-06250-x · Cited by 243 · see citing works
Milaneschi, Y., Lamers, F., Peyrot, W. J., Baune, B. T., Breen, G., Dehghan, A., Forstner, A. J., Grabe, H. J., Homuth, G., Kan, C., et al. (2017) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2017.3016 · Cited by 233 · see citing works
Genome-wide association study of MRI markers of cerebral small vessel disease in 42,310 participants
Persyn, E., Hanscombe, K. B., Howson, J. M. M., Lewis, C. M., Traylor, M., & Markus, H. S. (2020) · Nature Communications · doi:10.1038/s41467-020-15932-3 · Cited by 201 · see citing works
Justice, A. E., Winkler, T. W., Feitosa, M. F., Graff, M., Fisher, V. A., Young, K. L., Barata, L., Deng, X., Czajkowski, J., Hadley, D., et al. (2017) · Nature Communications · doi:10.1038/ncomms14977 · Cited by 207 · see citing works
The importance of gene–environment interactions in human obesity
Reddon, H., Guéant, J., & Meyre, D. (2016) · Clinical Science · doi:10.1042/cs20160221 · Cited by 198 · see citing works
Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits
Tachmazidou, I., Süveges, D., Min, J. L., Ritchie, G. R. S., Steinberg, J., Walter, K., Iotchkova, V., Schwartzentruber, J., Huang, J., Memari, Y., et al. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.04.014 · Cited by 188 · see citing works
A genome-wide association study of bitter and sweet beverage consumption
Zhong, V. W., Kuang, A., Danning, R., Kraft, P., van Dam, R. M., Chasman, D. I., & Cornelis, M. C. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz061 · Cited by 169 · see citing works
Self-citationMcCormick, N., O’Connor, M. J., Yokose, C., Merriman, T. R., Mount, D. B., Leong, A., & Choi, H. K. (2021) · Arthritis & Rheumatology · doi:10.1002/art.41779 · Cited by 173 · see citing works
Adiposity, metabolites, and colorectal cancer risk: Mendelian randomization study
Bull, C. J., Bell, J. A., Murphy, N., Sanderson, E. C. M., Smith, G. D., Timpson, N. J., Banbury, B. L., Albanes, D., Berndt, S. I., Bezieau, S., et al. (2020) · BMC Medicine · doi:10.1186/s12916-020-01855-9 · Cited by 167 · see citing works
Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots
Agrawal, S., Wang, M., Klarqvist, M. D. R., Smith, K., Shin, J. H., Dashti, H., Diamant, N., Choi, S. H., Jurgens, S. J., Ellinor, P. T., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30931-2 · Cited by 151 · see citing works
Genetic loci associated with heart rate variability and their effects on cardiac disease risk
Nolte, I. M., Muñoz, M. L., Tragante, V., Amare, A. T., Jansen, R., Vaez, A., von der Heyde, B., Avery, C. L., Bis, J. C., Dierckx, B., et al. (2017) · Nature Communications · doi:10.1038/ncomms15805 · Cited by 153 · see citing works
The genetic architecture of structural left–right asymmetry of the human brain
Sha, Z., Schijven, D., Carrión-Castillo, A., Joliot, M., Mazoyer, B. M., Fisher, S. E., Crivello, F., & Francks, C. (2021) · Nature Human Behaviour · doi:10.1038/s41562-021-01069-w · Cited by 136 · see citing works
Human Genetics of Addiction: New Insights and Future Directions
Hancock, D. B., Markunas, C. A., Bierut, L. J., & Johnson, E. O. (2018) · Current Psychiatry Reports · doi:10.1007/s11920-018-0873-3 · Cited by 142 · see citing works
Campos, A. I., García‐Marín, L. M., Byrne, E. M., Martin, N. G., Cuéllar-Partida, G., & Rentería, M. E. (2020) · Nature Communications · doi:10.1038/s41467-020-14625-1 · Cited by 136 · see citing works
the 23andMe Research Team, Sanchez-Roige, S., Fontanillas, P., Elson, S. L., Pandit, A., Schmidt, E. M., Foerster, J. R., Abecasis, G. R., Gray, J. C., de Wit, H., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-017-0032-x · Cited by 128 · see citing works
Hartwig, F. P., Tilling, K. M., Smith, G. D., Lawlor, D. A., & Borges, M. C. (2021) · International Journal of Epidemiology · doi:10.1093/ije/dyaa266 · Cited by 116 · see citing works
Adjustment for index event bias in genome-wide association studies of subsequent events.
Dudbridge, F., Allen, R. J., Sheehan, N. A., Schmidt, A. F., Lee, J. C., Jenkins, R. G., Wain, L. V., Hingorani, A. D., & Patel, R. S. (2019) · Nature Communications · doi:10.1038/s41467-019-09381-w · Cited by 115 · see citing works
A Robust Example of Collider Bias in a Genetic Association Study
Day, F. R., Loh, P., Scott, R. A., Ong, K. K., & Perry, J. R. B. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.12.019 · Cited by 113 · see citing works
Peyrot, W. J., & Price, A. L. (2021) · Nature Genetics · doi:10.1038/s41588-021-00787-1 · Cited by 106 · see citing works
Self-citationMuñoz, M., Pong‐Wong, R., Canela‐Xandri, O., Rawlik, K., Haley, C., & Tenesa, A. (2016) · Nature Genetics · doi:10.1038/ng.3618 · Cited by 108 · see citing works
Cadby, G., Giles, C., Melton, P. E., Huynh, K., Mellett, N. A., Duong, T., Nguyen, T. A., Cinel, M. A., Smith, A., Olshansky, G., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30875-7 · Cited by 104 · see citing works
Justice, A. E., Karaderi, T., Highland, H. M., Young, K. L., Graff, M., Lu, Y., Turcot, V., Auer, P. L., Fine, R. S., Guo, X., et al. (2019) · Nature Genetics · doi:10.1038/s41588-018-0334-2 · Cited by 98 · see citing works
Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat
Sung, Y. J., Përusse, L., Sarzynski, M. A., Fornage, M., Sidney, S. S., Sternfeld, B., Rice, T., Terry, J. G., Jacobs, D. R., Katzmarzyk, P. T., et al. (2015) · International Journal of Obesity · doi:10.1038/ijo.2015.217 · Cited by 97 · see citing works
Mina, T. H., Yew, Y. W., Ng, H. K., Sadhu, N., Wansaicheong, G. K. L., Dalan, R., Low, D. Y., Lam, B. C. C., Ríboli, E., Lee, E. S., et al. (2023) · The Lancet Regional Health - Western Pacific · doi:10.1016/j.lanwpc.2023.100710 · Cited by 97 · see citing works
Nature vs nurture in knee osteoarthritis – the importance of age, sex and body mass index
Magnusson, K., Turkiewicz, A., & Englund, M. (2019) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2018.12.018 · Cited by 92 · see citing works
Chan, Y., Salem, R. M., Hsu, Y.-H. H., McMahon, G., Pers, T. H., Vedantam, S., Esko, T., Guo, M. H., Lim, E. T., Franke, L., et al. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.02.018 · Cited by 81 · see citing works
Dolan, M. E., Charif, O. E., Wheeler, H. E., Gamazon, E. R., Ardeshir‐Rouhani‐Fard, S., Monahan, P. O., Feldman, D. R., Hamilton, R. J., Vaughn, D. J., Beard, C. J., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-3224 · Cited by 86 · see citing works
Lung function and cardiovascular disease: a two-sample Mendelian randomisation study
Higbee, D., Granell, R., Sanderson, E. C. M., Smith, G. D., & Dodd, J. W. (2021) · European Respiratory Journal · doi:10.1183/13993003.03196-2020 · Cited by 87 · see citing works
Circulating levels of micronutrients and risk of infections: a Mendelian randomization study
Flatby, H. M., Ravi, A., Damås, J. K., Solligård, E., & Rogne, T. (2023) · BMC Medicine · doi:10.1186/s12916-023-02780-3 · Cited by 87 · see citing works
Assessing the Causal Role of Body Mass Index on Cardiovascular Health in Young Adults
Wade, K. H., Chiesa, S. T., Hughes, A. D., Chaturvedi, N., Charakida, M., Rapala, A., Muthurangu, V., Khan, T. A., Finer, N., Sattar, N. A., et al. (2018) · Circulation · doi:10.1161/circulationaha.117.033278 · Cited by 83 · see citing works
Gallois, A., Mefford, J., Ko, A., Vaysse, A., Julienne, H., Ala‐Korpela, M., Laakso, M., Zaitlen, N., Pajukanta, P., & Aschard, H. (2019) · Nature Communications · doi:10.1038/s41467-019-12703-7 · Cited by 78 · see citing works
Self-citationWarrier, V., Stauffer, E.-M., Huang, Q. Q., Wigdor, E. M., Slob, E. A. W., Seidlitz, J., Ronan, L., Valk, S. L., Mallard, T. T., Grotzinger, A. D., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01475-y · Cited by 85 · see citing works
The genetic architecture and evolution of the human skeletal form
Kun, E., Javan, E. M., Smith, O. S., Gulamali, F. F., de la Fuente, J., Flynn, B. I., Vajrala, K., Trutner, Z. D., Jayakumar, P., Tucker–Drob, E. M., et al. (2023) · Science · doi:10.1126/science.adf8009 · Cited by 78 · see citing works
Wen, W., Kato, N., Hwang, J., Guo, X., Tabara, Y., Li, H., Dorajoo, R., Yang, X., Tsai, F., Li, S., et al. (2016) · Scientific Reports · doi:10.1038/srep17958 · Cited by 75 · see citing works
Mullin, B. H., Walsh, J. P., Zheng, H., Brown, S. J., Surdulescu, G. L., Curtis, C. J. C., Breen, G. D., Dudbridge, F., Richards, J. B., Spector, T. D., et al. (2016) · BMC Genomics · doi:10.1186/s12864-016-2481-0 · Cited by 74 · see citing works
Meng, X., Li, X., Timofeeva, M. N., He, Y., Spiliopoulou, A., Wei, W., Gifford, A., Wu, H., Varley, T., Joshi, P. K., et al. (2019) · International Journal of Epidemiology · doi:10.1093/ije/dyz182 · Cited by 72 · see citing works
Genetic study of multimodal imaging Alzheimer’s disease progression score implicates novel loci
Scelsi, M. A., Khan, R. R., Lorenzi, M., Christopher, L., Greicius, M. D., Schott, J. M., Ourselin, S., & Altmann, A. (2018) · Brain · doi:10.1093/brain/awy141 · Cited by 73 · see citing works
Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference
Corbin, L. J., Tan, V. Y., Hughes, D. A., Wade, K. H., Paul, D. S., Tansey, K. E., Butcher, F. C., Dudbridge, F., Howson, J. M. M., Jallow, M. W., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03109-y · Cited by 66 · see citing works
Ahlberg, G., Andreasen, L., Ghouse, J., Bertelsen, L., Bundgaard, H., Haunsø, S., Svendsen, J. H., & OLESEN, M. S. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab466 · Cited by 70 · see citing works
Community-wide genome sequencing reveals 30 years of Darwin’s finch evolution
Enbody, E. D., Sendell-Price, A. T., Sprehn, C. G., Rubin, C.-J., Visscher, P. M., Grant, B. R., Grant, P. R., & Andersson, L. (2023) · Science · doi:10.1126/science.adf6218 · Cited by 69 · see citing works
Zhu, Z., Li, J., Si, J., Ma, B., Shi, H., Lv, J., Cao, W., Guo, Y., Millwood, I. Y., Walters, R. G., et al. (2021) · European Respiratory Journal · doi:10.1183/13993003.00199-2021 · Cited by 61 · see citing works
Dahl, A., Thompson, M., An, U., Krebs, M. D., Appadurai, V., Border, R., Bacanu, S., Werge, T. M., Jonathan Flint, C., Schork, A. J., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01559-9 · Cited by 59 · see citing works
Kemp, J. P., Sayers, A. E., Smith, G. D., Tobias, J. H., & Evans, D. M. (2016) · International Journal of Epidemiology · doi:10.1093/ije/dyw079 · Cited by 57 · see citing works
Gorski, M., Rasheed, H., Teumer, A., Thomas, L. F., Graham, S. E., Sveinbjörnsson, G., Winkler, T. W., Günther, F., Stark, K. J., Chai, J. F., et al. (2022) · Kidney International · doi:10.1016/j.kint.2022.05.021 · Cited by 56 · see citing works
Akbari, P., Sosina, O. A., Bovijn, J., Landheer, K., Nielsen, J. B., Kim, M., Aykul, S., De, T., Haas, M. E., Hindy, G., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32398-7 · Cited by 56 · see citing works
Genetic effects on the commensal microbiota in inflammatory bowel disease patients
Aschard, H., Laville, V., Tchetgen, E. T., Knights, D., Imhann, F., Seksik, P., Zaitlen, N., Silverberg, M. S., Cosnes, J., Weersma, R. K., et al. (2019) · PLoS Genetics · doi:10.1371/journal.pgen.1008018 · Cited by 55 · see citing works
Self-citationHanscombe, K. B., Persyn, E., Traylor, M., Glanville, K. P., Hamer, M., Coleman, J. R. I., & Lewis, C. M. (2021) · Genome Medicine · doi:10.1186/s13073-021-00994-9 · Cited by 53 · see citing works
A phenome-wide comparative analysis of genetic discordance between obesity and type 2 diabetes
Coral, D., Fernandez-Tajes, J. J., Tsereteli, N., Pomares‐Millan, H., Fitipaldi, H., Mutie, P. M., Atabaki‐Pasdar, N., Kalamajski, S., Poveda, A., Miller‐Fleming, T. W., et al. (2023) · Nature Metabolism · doi:10.1038/s42255-022-00731-5 · Cited by 51 · see citing works
Rosoff, D. B., Kaminsky, Z. A., McIntosh, A. M., Smith, G. D., & Lohoff, F. W. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-01047-2 · Cited by 59 · see citing works
Dietary Factors and Endometrial Cancer Risk: A Mendelian Randomization Study
Wang, X. M., Glubb, D. M., & O’Mara, T. A. (2023) · Nutrients · doi:10.3390/nu15030603 · Cited by 55 · see citing works
Lawlor, D. A., Wade, K. H., Borges, M. C., Palmer, T., Hartwig, F. P., Hemani, G., & Bowden, J. (2019) · doi:10.31219/osf.io/6yzs7 · Cited by 50 · see citing works
Campos, A. I., Ingold, N., Huang, Y., Mitchell, B. L., Kho, P. F., Han, X., García‐Marín, L. M., Ong, J., Agee, M., Aslibekyan, S., et al. (2022) · SLEEP · doi:10.1093/sleep/zsac308 · Cited by 51 · see citing works
Winkler, T. W., Günther, F., Höllerer, S., Zimmermann, M. E., Loos, R. J. F., Kutalik, Z., & Heid, I. M. (2018) · Nature Communications · doi:10.1038/s41467-018-04124-9 · Cited by 51 · see citing works
Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity
Yaghootkar, H., Zhang, Y., Spracklen, C. N., Karaderi, T., Huang, L. O., Bradfield, J. P., Schurmann, C., Fine, R. S., Preuss, M. H., Kutalik, Z., et al. (2020) · Diabetes · doi:10.2337/db20-0070 · Cited by 51 · see citing works
Deep learning of left atrial structure and function provides link to atrial fibrillation risk
Pirruccello, J. P., Achille, P. D., Choi, S. H., Rämö, J. T., Khurshid, S. S., Nekoui, M., Jurgens, S. J., Nauffal, V. D., Kany, S., FinnGen, et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48229-w · Cited by 48 · see citing works
Tsilidis, K. K., Papadimitriou, N., Dimou, N. L., Gill, D., Lewis, S. J., Martin, R. M., Murphy, N., Markozannes, G., Zuber, V., Cross, A. J., et al. (2021) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqab003 · Cited by 46 · see citing works
Niarchou, M., Byrne, E. M., Trzaskowski, M., Sidorenko, J., Kemper, K. E., McGrath, J. J., O’Donovan, M. C., Owen, M. J., & Wray, N. R. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0688-y · Cited by 45 · see citing works
Causal link between lipid profile and bone mineral density: A Mendelian randomization study
Yang, X., Cui, Z., Zhang, H., Wei, X., Feng, G.-J., Liu, L., Liu, Y., Pei, Y., & Zhang, L. (2019) · Bone · doi:10.1016/j.bone.2019.05.037 · Cited by 44 · see citing works
Quantifying the extent to which index event biases influence large genetic association studies
Yaghootkar, H., Bancks, M. P., Jones, S. E., McDaid, A. F., Beaumont, R. N., Donnelly, L. A., Wood, A. R., Campbell, A. I., Tyrrell, J., Hocking, L. J., et al. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw433 · Cited by 42 · see citing works
Meta-Analysis of Genomewide Association Studies Reveals Genetic Variants for Hip Bone Geometry
Hsu, Y., Estrada, K., Εvangelou, Ε., Ackert‐Bicknell, C. L., Åkesson, K., Beck, T., Brown, S. J., Capellini, T. D., Carbone, L. D., Cauley, J. A., et al. (2019) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3698 · Cited by 40 · see citing works
Genetic Pathways Underlying Individual Differences in Regular Physical Activity
de Geus, E. J. C. (2022) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000305 · Cited by 39 · see citing works
Kamura, Y., Iwata, M., Maeda, S., Shinmura, S., Koshimizu, Y., Honoki, H., Fukuda, K., Ishiki, M., Usui, I., Fukushima, Y., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0165523 · Cited by 38 · see citing works
Relationships between estimated autozygosity and complex traits in the UK Biobank
Johnson, E. C., Evans, L. M., & Keller, M. C. (2018) · PLoS Genetics · doi:10.1371/journal.pgen.1007556 · Cited by 38 · see citing works
Multivariable MR Can Mitigate Bias in Two‐Sample MR Using Covariable‐Adjusted Summary Associations
Gilbody, J., Borges, M. C., Smith, G. D., & Sanderson, E. C. M. (2025) · Genetic Epidemiology · doi:10.1002/gepi.22606 · Cited by 37 · see citing works
Carrión-Castillo, A., Pepe, A., Kong, X., Fisher, S. E., Mazoyer, B. M., Tzourio‐Mazoyer, N., Crivello, F., & Francks, C. (2019) · Cortex · doi:10.1016/j.cortex.2019.11.006 · Cited by 35 · see citing works
Merrick, L. F., Burke, A. B., Zhang, Z., & Carter, A. H. (2022) · Frontiers in Plant Science · doi:10.3389/fpls.2021.772907 · Cited by 36 · see citing works
Winkler, T. W., Günther, F., Höllerer, S., Zimmermann, M. E., Loos, R. J. F., Kutalik, Z., & Heid, I. M. (2018) · Nature Communications · doi:10.1038/s41467-018-05088-6 · Cited by 35 · see citing works
Kidney function and obstructive lung disease: a bidirectional Mendelian randomisation study
Park, S., Lee, S., Kim, Y., Cho, S., Kim, K., Kim, Y. C., Han, S. S., Lee, H., Lee, J. P., Joo, K. W., et al. (2021) · European Respiratory Journal · doi:10.1183/13993003.00848-2021 · Cited by 34 · see citing works
Grotzinger, A. D., Mallard, T. T., Liu, Z., Seidlitz, J., Ge, T., & Smoller, J. W. (2023) · Nature Communications · doi:10.1038/s41467-023-36605-x · Cited by 34 · see citing works
Zhao, J. V., Liu, F., Schooling, C. M., Li, J., Gu, D., & Lu, X. (2022) · Diabetologia · doi:10.1007/s00125-021-05645-7 · Cited by 34 · see citing works
Adjusting for principal components can induce collider bias in genome-wide association studies
Grinde, K. E., Browning, B. L., Reiner, A. P., Thornton, T. A., & Browning, S. R. (2024) · PLoS Genetics · doi:10.1371/journal.pgen.1011242 · Cited by 33 · see citing works
Rajagopal, V. M., Ganna, A., Coleman, J. R. I., Allegrini, A. G., Voloudakis, G., Grove, J., Als, T. D., Horsdal, H. T., Petersen, L. V., Appadurai, V., et al. (2023) · Scientific Reports · doi:10.1038/s41598-022-26845-0 · Cited by 33 · see citing works
Yau, M. S., Demissie, S., Zhou, Y., Anderson, D., Lorbergs, A. L., Kiel, D. P., Allaire, B., Yang, L., Cupples, L. A., Travison, T. G., et al. (2016) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2925 · Cited by 32 · see citing works
Somatic mutational profiles and germline polygenic risk scores in human cancer
Liu, Y., Gusev, A., Heng, Y. J., Alexandrov, L. B., & Kraft, P. L. (2022) · Genome Medicine · doi:10.1186/s13073-022-01016-y · Cited by 28 · see citing works
Self-citationGenomic Prediction of Autogamous and Allogamous Plants by SNPs and Haplotypes
Matias, F. I., Galli, G., Granato, Í. S. C., & Fritsche‐Neto, R. (2017) · Crop Science · doi:10.2135/cropsci2017.01.0022 · Cited by 26 · see citing works
Adjusting for collider bias in genetic association studies using instrumental variable methods
Cai, S., Hartley, A. E., Mahmoud, O., Tilling, K. M., & Dudbridge, F. (2022) · Genetic Epidemiology · doi:10.1002/gepi.22455 · Cited by 28 · see citing works
Covariate selection for association screening in multiphenotype genetic studies
Aschard, H., Guillemot, V., Vilhjálmsson, B. J., Patel, C. J., Skurnik, D., Ye, C., Wolpin, B. M., Kraft, P. L., & Zaitlen, N. (2017) · Nature Genetics · doi:10.1038/ng.3975 · Cited by 25 · see citing works
Self-citationLow‐Kam, C., Rhainds, D., Lo, K. S., Barhdadi, A., Boulé, M., Alem, S., Pedneault-Gagnon, V., Rhéaume, É., Dubé, M., Busseuil, D., et al. (2018) · Journal of the American Heart Association · doi:10.1161/jaha.118.009545 · Cited by 28 · see citing works
Qiu, Y., Liu, Q., Luo, Y., Chen, J., Zheng, Q., Xie, Y., & Cao, Y. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1287463 · Cited by 30 · see citing works
Verhoef, E., Demontis, D., Burgess, S., Shapland, C. Y., Dale, P. S., Okbay, A., Neale, B. M., Faraone, S. V., Agerbo, E., Als, T. D., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-018-0324-2 · Cited by 28 · see citing works
Mendelian randomization highlights the causal association of obesity with periodontal diseases
Dong, J., Gong, Y., Chu, T., Wu, L., Li, S., Deng, H., Hu, R., & Wang, Y. (2022) · Journal Of Clinical Periodontology · doi:10.1111/jcpe.13640 · Cited by 27 · see citing works
- Authors
- Aschard, H., Vilhjálmsson, B. J., Joshi, A. D., Price, A. L., & Kraft, P.
- Affiliations
- Harvard University (US)
- Corresponding author
- Aschard, Hugues
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 96
- Issue
- 2
- Pages
- 329-339
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC4320269
- OpenAlex
- W1996682563
- Cited by
- 287
- References
- 40
- Citations by year
- 2026: 16 · 2025: 25 · 2024: 30 · 2023: 27 · 2022: 30 · 2021: 33 · 2020: 26 · 2019: 24 · 2018: 26 · 2017: 20 · 2016: 22 · 2015: 8
- FWCI
- 17.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- National Human Genome Research Institute (R03HG006720)
- National Cancer Institute (U19CA148065)
- National Institute of Environmental Health Sciences (R21ES020754)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- genome-wide association study, correlated traits, false positives, waist-to-hip ratio, waist circumference, body mass index, confounding
- MeSH terms
- Computer Simulation, Humans, Models, Genetic, Genetic Variation, Body Mass Index, Quantitative Trait, Heritable, Waist-Hip Ratio, Waist Circumference, Genome-Wide Association Study
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