{"department":[{"_id":"NiBa"}],"OA_place":"publisher","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","language":[{"iso":"eng"}],"volume":231,"date_published":"2025-12-01T00:00:00Z","citation":{"short":"J.J. Berg, X. Li, K. Riall, L. Hayward, G. Sella, Genetics 231 (2025).","mla":"Berg, Jeremy J., et al. “Mutation–Selection–Drift Balance Models of Complex Diseases.” <i>Genetics</i>, vol. 231, no. 4, iyaf220, Oxford University Press, 2025, doi:<a href=\"https://doi.org/10.1093/genetics/iyaf220\">10.1093/genetics/iyaf220</a>.","chicago":"Berg, Jeremy J., Xinyi Li, Kellen Riall, Laura Hayward, and Guy Sella. “Mutation–Selection–Drift Balance Models of Complex Diseases.” <i>Genetics</i>. Oxford University Press, 2025. <a href=\"https://doi.org/10.1093/genetics/iyaf220\">https://doi.org/10.1093/genetics/iyaf220</a>.","ama":"Berg JJ, Li X, Riall K, Hayward L, Sella G. Mutation–selection–drift balance models of complex diseases. <i>Genetics</i>. 2025;231(4). doi:<a href=\"https://doi.org/10.1093/genetics/iyaf220\">10.1093/genetics/iyaf220</a>","ieee":"J. J. Berg, X. Li, K. Riall, L. Hayward, and G. Sella, “Mutation–selection–drift balance models of complex diseases,” <i>Genetics</i>, vol. 231, no. 4. Oxford University Press, 2025.","ista":"Berg JJ, Li X, Riall K, Hayward L, Sella G. 2025. Mutation–selection–drift balance models of complex diseases. Genetics. 231(4), iyaf220.","apa":"Berg, J. J., Li, X., Riall, K., Hayward, L., &#38; Sella, G. (2025). Mutation–selection–drift balance models of complex diseases. <i>Genetics</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/genetics/iyaf220\">https://doi.org/10.1093/genetics/iyaf220</a>"},"publication_status":"published","month":"12","acknowledgement":"We thank Nick Barton, Magnus Nordborg, John Novembre, Molly Przeworski, and Himani Sachdeva for many helpful discussions and for comments on the manuscript, and we thank Joshua Schraiber and 2 anonymous reviewers for comments on the manuscript. We also thank members of the Sella, Przeworski and Andolfatto labs at Columbia University, and the Berg, Novembre and Steinrücken labs at the University of Chicago, for feedback on the work at various stages. This work was completed in part with resources provided by the University of Chicago's Research Computing Center. This work was supported by National Institutes of Health F32 grant GM126787 and R35 grant GM151257 to J.J.B. and National Institutes of Health R01 grant GM115889 to G.S.","oa":1,"file_date_updated":"2025-12-29T11:27:51Z","article_number":"iyaf220","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","quality_controlled":"1","external_id":{"pmid":["41073879"]},"intvolume":"       231","scopus_import":"1","article_type":"original","year":"2025","doi":"10.1093/genetics/iyaf220","abstract":[{"lang":"eng","text":"Genetic variation that influences complex disease susceptibility is introduced into the population by mutation and removed by natural selection and genetic drift. This mutation–selection–drift balance (MSDB) shapes the prevalence of a disease and its genetic architecture. To date, however, MSDB has been modeled only for monogenic (Mendelian) diseases. Here, we develop an MSDB model for complex disease susceptibility: we assume that genotype relates to disease risk according to the canonical liability threshold model and that the selection on variants affecting risk stems from the fitness cost of the disease. We focus on diseases that are highly polygenic, entail a substantial fitness cost, and are neither extremely common in the population nor exceedingly rare. The comparison of model predictions with genome-wide association studies and other observations in humans indicates that common genetic variation affecting complex disease susceptibility is little affected by directional selection and instead shaped by pleiotropic stabilizing selection on other traits. In turn, directional selection may exert a more substantial effect on rare, large-effect variants. Our results also suggest that current estimates of disease heritability are likely biased. The model thus provides a better understanding of the evolutionary processes that shape the architecture and prevalence of complex diseases."}],"date_updated":"2025-12-29T11:29:16Z","_id":"20848","author":[{"last_name":"Berg","first_name":"Jeremy J.","full_name":"Berg, Jeremy J."},{"last_name":"Li","first_name":"Xinyi","full_name":"Li, Xinyi"},{"last_name":"Riall","first_name":"Kellen","full_name":"Riall, Kellen"},{"id":"fc885ee5-24bf-11eb-ad7b-bcc5104c0c1b","full_name":"Hayward, Laura","first_name":"Laura","last_name":"Hayward"},{"full_name":"Sella, Guy","first_name":"Guy","last_name":"Sella"}],"publisher":"Oxford University Press","date_created":"2025-12-21T23:01:34Z","day":"01","title":"Mutation–selection–drift balance models of complex diseases","pmid":1,"issue":"4","OA_type":"hybrid","article_processing_charge":"Yes (in subscription journal)","file":[{"checksum":"b02eb6b78028b8bef435edc8435a8468","file_name":"2025_Genetics_Berg.pdf","file_size":1182339,"creator":"dernst","content_type":"application/pdf","date_created":"2025-12-29T11:27:51Z","file_id":"20863","access_level":"open_access","relation":"main_file","success":1,"date_updated":"2025-12-29T11:27:51Z"}],"publication":"Genetics","status":"public","tmp":{"image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)"},"type":"journal_article","oa_version":"Published Version","has_accepted_license":"1","publication_identifier":{"eissn":["1943-2631"],"issn":["0016-6731"]},"ddc":["570"]}