{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T02:30:58Z","timestamp":1784687458766,"version":"3.55.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Genetic pleiotropy is when a single gene influences more than one trait. Detecting pleiotropy and understanding its causes can improve the biological understanding of a gene in multiple ways, yet current multivariate methods to evaluate pleiotropy test the null hypothesis that none of the traits are associated with a variant; departures from the null could be driven by just one associated trait. A formal test of pleiotropy should assume a null hypothesis that one or no traits are associated with a genetic variant. For the special case of two traits, one can construct this null hypothesis based on the intersection-union (IU) test, which rejects the null hypothesis only if the null hypotheses of no association for both traits are rejected. To allow for more than two traits, we developed a new likelihood-ratio test for pleiotropy. We then extended the testing framework to a sequential approach to test the null hypothesis that k+1 traits are associated, given that the null of k traits are associated was rejected. This provides a formal testing framework to determine the number of traits associated with a genetic variant, while accounting for correlations among the traits. By simulations, we illustrate the type I error rate and power of our new methods; describe how they are influenced by sample size, the number of traits, and the trait correlations; and apply the new methods to multivariate immune phenotypes in response to smallpox vaccination. Our new approach provides a quantitative assessment of pleiotropy, enhancing current analytic practice.<\/jats:p>","DOI":"10.1534\/genetics.116.189308","type":"journal-article","created":{"date-parts":[[2016,8,16]],"date-time":"2016-08-16T01:03:20Z","timestamp":1471309400000},"page":"483-497","source":"Crossref","is-referenced-by-count":54,"title":["Statistical Methods for Testing Genetic Pleiotropy"],"prefix":"10.1093","volume":"204","author":[{"given":"Daniel J","family":"Schaid","sequence":"first","affiliation":[{"name":"Department of Health Sciences Research , Mayo Clinic, Rochester, Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingwei","family":"Tong","sequence":"additional","affiliation":[{"name":"School of Statistics , Beijing Normal University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Larrabee","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research , Mayo Clinic, Rochester, Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Mayo Clinic Vaccine Research Group , Mayo Clinic, Rochester, Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A","family":"Poland","sequence":"additional","affiliation":[{"name":"Mayo Clinic Vaccine Research Group , Mayo Clinic, Rochester, Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason P","family":"Sinnwell","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research , Mayo Clinic, Rochester, Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,10,1]]},"reference":[{"issue":"3","key":"2023030909022503200_","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2307\/3002000","article-title":"Limitations of the application of fourfold table analysis to hospital data","volume":"2","author":"Berkson","year":"1946","journal-title":"Biom. 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