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Gene\u2013environment\u2010wide interaction studies (GEWIS) provide a means to identify the interactions between genetic variation and environmental exposures that underlie disease risk. However, current GEWIS methods lack the capability to adjust for the potentially complex correlations in studies with varying degrees of relationships (both known and unknown) among individuals in admixed populations. We developed novel generalized estimating equation (GEE) based methods\u2014GEE\u2010adaptive and GEE\u2010joint\u2014to account for phenotypic correlations due to kinship while accounting for covariates, including, measures of genome\u2010wide ancestry. In simulation studies of admixed individuals, both methods controlled family\u2010wise error rates, an advantage over the case\u2010only approach. They demonstrated higher power than traditional case\u2013control methods across a wide range of underlying alternative hypotheses, especially where both marginal and interaction effects were present. We applied the proposed method to conduct a GEWIS of a known sarcoidosis risk factor (insecticide exposure) and risk of sarcoidosis in African Americans and identified two novel loci with suggestive evidence of G\u2009\u00d7\u2009E interaction.<\/jats:p>","DOI":"10.1002\/gepi.22196","type":"journal-article","created":{"date-parts":[[2019,2,22]],"date-time":"2019-02-22T13:06:00Z","timestamp":1550840760000},"page":"414-426","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Extended methods for gene\u2013environment\u2010wide interaction scans in studies of admixed individuals with varying degrees of relationships"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1240-3515","authenticated-orcid":false,"given":"Yalei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Public Health Sciences Henry Ford Health System Detroit Michigan"},{"name":"Center for Bioinformatics Henry Ford Health System Detroit Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indra","family":"Adrianto","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences Henry Ford Health System Detroit Michigan"},{"name":"Center for Bioinformatics Henry Ford Health System Detroit Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Iannuzzi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Northwell Staten Island University Hospital Staten Island, New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori","family":"Garman","sequence":"additional","affiliation":[{"name":"Arthritis and Clinical Immunology Research Program Oklahoma Medical Research Foundation Oklahoma City Oklahoma"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney G.","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Arthritis and Clinical Immunology Research Program Oklahoma Medical Research Foundation Oklahoma City Oklahoma"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin A.","family":"Rybicki","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences Henry Ford Health System Detroit Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert M.","family":"Levin","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences Henry Ford Health System Detroit Michigan"},{"name":"Center for Bioinformatics Henry Ford Health System Detroit Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5931-3058","authenticated-orcid":false,"given":"Jia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences Henry Ford Health System Detroit Michigan"},{"name":"Center for Bioinformatics Henry Ford Health System Detroit Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,22]]},"reference":[{"key":"e_1_2_6_1_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0043907"},{"key":"e_1_2_6_1_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10709-007-9181-2"},{"key":"e_1_2_6_1_4_1","doi-asserted-by":"publisher","DOI":"10.2307\/2529826"},{"key":"e_1_2_6_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.02.012"},{"key":"e_1_2_6_1_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2653"},{"key":"e_1_2_6_1_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/ass044"},{"key":"e_1_2_6_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.07.014"},{"key":"e_1_2_6_1_9_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v040.i08"},{"key":"e_1_2_6_1_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1333"},{"key":"e_1_2_6_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.12.022"},{"key":"e_1_2_6_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2660(08)00602-0"},{"key":"e_1_2_6_1_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.642"},{"key":"e_1_2_6_1_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0108384"},{"key":"e_1_2_6_1_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21610"},{"key":"e_1_2_6_1_16_1","unstructured":"Huber P. 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