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7. Genetic analyses identify widespread sex-differential participation bias

Author

Pirastu N., Cordioli M., Nandakumar P., Mignogna G., Abdellaoui A., Hollis B., Kanai M., Rajagopal V. M., Parolo P. D. B., Baya N., Carey C. E., Karjalainen J., Als T. D., Van der Zee M. D., Day F. R., Ong K. K., Agee M., Aslibekyan S., Bell R. K., Bryc K., Clark S. K., Elson S. L., Fletez-Brant K., Fontanillas P., Furlotte N. A., Gandhi P. M., Heilbron K., Hicks B., Huber K. E., Jewett E. M., Jiang Y., Kleinman A., Lin K. -H., Litterman N. K., Luff M. K., McIntyre M. H., McManus K. F., Mountain J. L., Mozaffari S. V., Noblin E. S., Northover C. A. M., O'Connell J., Petrakovitz A. A., Pitts S. J., Poznik G. D., Sathirapongsasuti J. F., Shelton J. F., Shringarpure S., Tian C., Tung J. Y., Tunney R. J., Vacic V., Wang X., Zare A., Mortensen P. B., Mors O., Werge T., Nordentoft M., Hougaard D. M., Bybjerg-Grauholm J., Baekvad-Hansen M., Morisaki T., de Geus E., Bellocco R., Okada Y., Borglum A. D., Joshi P., Auton A., Hinds D., Neale B. M., Walters R. K., Nivard M. G., Perry J. R. B., Ganna A., Pirastu, N, Cordioli, M, Nandakumar, P, Mignogna, G, Abdellaoui, A, Hollis, B, Kanai, M, Rajagopal, V, Parolo, P, Baya, N, Carey, C, Karjalainen, J, Als, T, Van der Zee, M, Day, F, Ong, K, Agee, M, Aslibekyan, S, Bell, R, Bryc, K, Clark, S, Elson, S, Fletez-Brant, K, Fontanillas, P, Furlotte, N, Gandhi, P, Heilbron, K, Hicks, B, Huber, K, Jewett, E, Jiang, Y, Kleinman, A, Lin, K, Litterman, N, Luff, M, Mcintyre, M, Mcmanus, K, Mountain, J, Mozaffari, S, Noblin, E, Northover, C, O'Connell, J, Petrakovitz, A, Pitts, S, Poznik, G, Sathirapongsasuti, J, Shelton, J, Shringarpure, S, Tian, C, Tung, J, Tunney, R, Vacic, V, Wang, X, Zare, A, Mortensen, P, Mors, O, Werge, T, Nordentoft, M, Hougaard, D, Bybjerg-Grauholm, J, Baekvad-Hansen, M, Morisaki, T, de Geus, E, Bellocco, R, Okada, Y, Borglum, A, Joshi, P, Auton, A, Hinds, D, Neale, B, Walters, R, Nivard, M, Perry, J, Ganna, A, Biological Psychology, APH - Personalized Medicine, APH - Mental Health, and Adult Psychiatry

Subjects
Adult, Inheritance Pattern, Male, Sex Characteristics, Inheritance Patterns, Sex Characteristic, Polymorphism, Single Nucleotide, Article, United Kingdom, Bias, Genetic Loci, Sample Size, Bia, Artifact, Biological Specimen Bank, Humans, Chromosomes, Human, Female, Artifacts, Biological Specimen Banks, Genome-Wide Association Study, Human
Abstract

Genetic association results are often interpreted with the assumption that study participation does not affect downstream analyses. Understanding the genetic basis of participation bias is challenging since it requires the genotypes of unseen individuals. Here we demonstrate that it is possible to estimate comparative biases by performing a genome-wide association study contrasting one subgroup versus another. For example, we showed that sex exhibits artifactual autosomal heritability in the presence of sex-differential participation bias. By performing a genome-wide association study of sex in approximately 3.3 million males and females, we identified over 158 autosomal loci spuriously associated with sex and highlighted complex traits underpinning differences in study participation between the sexes. For example, the body mass index-increasing allele at FTO was observed at higher frequency in males compared to females (odds ratio = 1.02, P = 4.4 × 10-36). Finally, we demonstrated how these biases can potentially lead to incorrect inferences in downstream analyses and propose a conceptual framework for addressing such biases. Our findings highlight a new challenge that genetic studies may face as sample sizes continue to grow.

Published
2021

14. Genetic analyses identify widespread sex-differential participation bias

Author

Pirastu, N, Cordioli, M, Nandakumar, P, Mignogna, G, Abdellaoui, A, Hollis, B, Kanai, M, Rajagopal, V, Parolo, P, Baya, N, Carey, C, Karjalainen, J, Als, T, Van der Zee, M, Day, F, Ong, K, Agee, M, Aslibekyan, S, Bell, R, Bryc, K, Clark, S, Elson, S, Fletez-Brant, K, Fontanillas, P, Furlotte, N, Gandhi, P, Heilbron, K, Hicks, B, Huber, K, Jewett, E, Jiang, Y, Kleinman, A, Lin, K, Litterman, N, Luff, M, Mcintyre, M, Mcmanus, K, Mountain, J, Mozaffari, S, Noblin, E, Northover, C, O'Connell, J, Petrakovitz, A, Pitts, S, Poznik, G, Sathirapongsasuti, J, Shelton, J, Shringarpure, S, Tian, C, Tung, J, Tunney, R, Vacic, V, Wang, X, Zare, A, Mortensen, P, Mors, O, Werge, T, Nordentoft, M, Hougaard, D, Bybjerg-Grauholm, J, Baekvad-Hansen, M, Morisaki, T, de Geus, E, Bellocco, R, Okada, Y, Borglum, A, Joshi, P, Auton, A, Hinds, D, Neale, B, Walters, R, Nivard, M, Perry, J, Ganna, A, Pirastu N., Cordioli M., Nandakumar P., Mignogna G., Abdellaoui A., Hollis B., Kanai M., Rajagopal V. M., Parolo P. D. B., Baya N., Carey C. E., Karjalainen J., Als T. D., Van der Zee M. D., Day F. R., Ong K. K., Agee M., Aslibekyan S., Bell R. K., Bryc K., Clark S. K., Elson S. L., Fletez-Brant K., Fontanillas P., Furlotte N. A., Gandhi P. M., Heilbron K., Hicks B., Huber K. E., Jewett E. M., Jiang Y., Kleinman A., Lin K. -H., Litterman N. K., Luff M. K., McIntyre M. H., McManus K. F., Mountain J. L., Mozaffari S. V., Noblin E. S., Northover C. A. M., O'Connell J., Petrakovitz A. A., Pitts S. J., Poznik G. D., Sathirapongsasuti J. F., Shelton J. F., Shringarpure S., Tian C., Tung J. Y., Tunney R. J., Vacic V., Wang X., Zare A., Mortensen P. B., Mors O., Werge T., Nordentoft M., Hougaard D. M., Bybjerg-Grauholm J., Baekvad-Hansen M., Morisaki T., de Geus E., Bellocco R., Okada Y., Borglum A. D., Joshi P., Auton A., Hinds D., Neale B. M., Walters R. K., Nivard M. G., Perry J. R. B., Ganna A., Pirastu, N, Cordioli, M, Nandakumar, P, Mignogna, G, Abdellaoui, A, Hollis, B, Kanai, M, Rajagopal, V, Parolo, P, Baya, N, Carey, C, Karjalainen, J, Als, T, Van der Zee, M, Day, F, Ong, K, Agee, M, Aslibekyan, S, Bell, R, Bryc, K, Clark, S, Elson, S, Fletez-Brant, K, Fontanillas, P, Furlotte, N, Gandhi, P, Heilbron, K, Hicks, B, Huber, K, Jewett, E, Jiang, Y, Kleinman, A, Lin, K, Litterman, N, Luff, M, Mcintyre, M, Mcmanus, K, Mountain, J, Mozaffari, S, Noblin, E, Northover, C, O'Connell, J, Petrakovitz, A, Pitts, S, Poznik, G, Sathirapongsasuti, J, Shelton, J, Shringarpure, S, Tian, C, Tung, J, Tunney, R, Vacic, V, Wang, X, Zare, A, Mortensen, P, Mors, O, Werge, T, Nordentoft, M, Hougaard, D, Bybjerg-Grauholm, J, Baekvad-Hansen, M, Morisaki, T, de Geus, E, Bellocco, R, Okada, Y, Borglum, A, Joshi, P, Auton, A, Hinds, D, Neale, B, Walters, R, Nivard, M, Perry, J, Ganna, A, Pirastu N., Cordioli M., Nandakumar P., Mignogna G., Abdellaoui A., Hollis B., Kanai M., Rajagopal V. M., Parolo P. D. B., Baya N., Carey C. E., Karjalainen J., Als T. D., Van der Zee M. D., Day F. R., Ong K. K., Agee M., Aslibekyan S., Bell R. K., Bryc K., Clark S. K., Elson S. L., Fletez-Brant K., Fontanillas P., Furlotte N. A., Gandhi P. M., Heilbron K., Hicks B., Huber K. E., Jewett E. M., Jiang Y., Kleinman A., Lin K. -H., Litterman N. K., Luff M. K., McIntyre M. H., McManus K. F., Mountain J. L., Mozaffari S. V., Noblin E. S., Northover C. A. M., O'Connell J., Petrakovitz A. A., Pitts S. J., Poznik G. D., Sathirapongsasuti J. F., Shelton J. F., Shringarpure S., Tian C., Tung J. Y., Tunney R. J., Vacic V., Wang X., Zare A., Mortensen P. B., Mors O., Werge T., Nordentoft M., Hougaard D. M., Bybjerg-Grauholm J., Baekvad-Hansen M., Morisaki T., de Geus E., Bellocco R., Okada Y., Borglum A. D., Joshi P., Auton A., Hinds D., Neale B. M., Walters R. K., Nivard M. G., Perry J. R. B., and Ganna A.

Abstract

Genetic association results are often interpreted with the assumption that study participation does not affect downstream analyses. Understanding the genetic basis of participation bias is challenging since it requires the genotypes of unseen individuals. Here we demonstrate that it is possible to estimate comparative biases by performing a genome-wide association study contrasting one subgroup versus another. For example, we showed that sex exhibits artifactual autosomal heritability in the presence of sex-differential participation bias. By performing a genome-wide association study of sex in approximately 3.3 million males and females, we identified over 158 autosomal loci spuriously associated with sex and highlighted complex traits underpinning differences in study participation between the sexes. For example, the body mass index–increasing allele at FTO was observed at higher frequency in males compared to females (odds ratio = 1.02, P = 4.4 × 10−36). Finally, we demonstrated how these biases can potentially lead to incorrect inferences in downstream analyses and propose a conceptual framework for addressing such biases. Our findings highlight a new challenge that genetic studies may face as sample sizes continue to grow.

Published
2021

45. Safety and efficacy of laparoscopic near‐total colectomy and ileo‐distal sigmoid anastomosis as a modification of total colectomy and ileorectal anastomosis for prophylactic surgery in patients with adenomatous polyposis syndromes: a comparative study

Author

Anele, C. C., primary, Nachiappan, S., additional, Sinha, A., additional, Cuthill, V., additional, Jenkins, J. T., additional, Clark, S. K., additional, Latchford, A., additional, and Faiz, O. D., additional

Published
2020
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48. Peutz–Jeghers syndrome: a systematic review and recommendations for management

Author

Beggs, A D, Latchford, A R, Vasen, H F, Moslein, G, Alonso, A, Aretz, S, Bertario, L, Blanco, I, Bülow, S, Burn, J, Capella, G, Colas, C, Friedl, W, Møller, P, Hes, F J, Järvinen, H, Mecklin, J-P, Nagengast, F M, Parc, Y, Phillips, R K, Hyer, W, Ponz de Leon, M, Renkonen-Sinisalo, L, Sampson, J R, Stormorken, A, Tejpar, S, Thomas, H J, Wijnen, J T, Clark, S K, and Hodgson, S V

Published
2010
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