{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:33:43Z","timestamp":1772138023404,"version":"3.50.1"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T00:00:00Z","timestamp":1701302400000},"content-version":"vor","delay-in-days":8,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R56AG069118"],"award-info":[{"award-number":["R56AG069118"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R56AG066889"],"award-info":[{"award-number":["R56AG066889"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R56AG059756"],"award-info":[{"award-number":["R56AG059756"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U19AG074865"],"award-info":[{"award-number":["U19AG074865"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG082009"],"award-info":[{"award-number":["R01AG082009"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The performances of popular genome-wide association study (GWAS) models have not been examined yet in a consistent manner under the scenario of genetic admixture, which introduces several challenging aspects: heterogeneity of minor allele frequency (MAF), wide spectrum of case\u2013control ratio, varying effect sizes, etc.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We generated a cohort of synthetic individuals (N\u2009=\u200919\u00a0234) that simulates (i) a large sample size; (ii) two-way admixture (Native American and European ancestry) and (iii) a binary phenotype. We then benchmarked three popular GWAS tools [generalized linear mixed model associated test (GMMAT), scalable and accurate implementation of generalized mixed model (SAIGE) and Tractor] by computing inflation factors and power calculations under different MAFs, case\u2013control ratios, sample sizes and varying ancestry proportions. We also employed a cohort of Peruvians (N\u2009=\u2009249) to further examine the performances of the testing models on (i) real genetic and phenotype data and (ii) small sample sizes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the synthetic cohort, SAIGE performed better than GMMAT and Tractor in terms of type-I error rate, especially under severe unbalanced case\u2013control ratio. On the contrary, power analysis identified Tractor as the best method to pinpoint ancestry-specific causal variants but showed decreased power when the effect size displayed limited heterogeneity between ancestries. In the Peruvian cohort, only Tractor identified two suggestive loci (P-value $\\le 1\\ast{10}^{-5}$) associated with Native American ancestry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The current study illustrates best practice and limitations for available GWAS tools under the scenario of genetic admixture. Incorporating local ancestry in GWAS analyses boosts power, although careful consideration of complex scenarios (small sample sizes, imbalance case\u2013control ratio, MAF heterogeneity) is needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bib\/bbad437","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T06:30:58Z","timestamp":1699511458000},"source":"Crossref","is-referenced-by-count":14,"title":["A benchmark study on current GWAS models in admixed populations"],"prefix":"10.1093","volume":"25","author":[{"given":"Zikun","family":"Yang","sequence":"first","affiliation":[{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain , College of Physicians and Surgeons, , 630 West 168th Street, New York, NY 10032 , USA"},{"name":"Columbia University , College of Physicians and Surgeons, , 630 West 168th Street, New York, NY 10032 , USA"},{"name":"The Gertrude H. Sergievsky Center , College of Physicians and Surgeons, , 630 West 168th Street, New York, NY 10032 , USA"},{"name":"Columbia University , College of Physicians and Surgeons, , 630 West 168th Street, New York, NY 10032 , USA"}]},{"given":"Basilio","family":"Cieza","sequence":"additional","affiliation":[{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain , College of Physicians and Surgeons, , 630 West 168th Street, New York, NY 10032 , USA"},{"name":"Columbia University , College of Physicians and Surgeons, , 630 West 168th Street, New York, NY 10032 , USA"},{"name":"The Gertrude H. Sergievsky Center , College of Physicians and Surgeons, , 630 West 168th Street, New York, NY 10032 , USA"},{"name":"Columbia University , College of Physicians and Surgeons, , 630 West 168th Street, New York, NY 10032 , USA"}]},{"given":"Dolly","family":"Reyes-Dumeyer","sequence":"additional","affiliation":[{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain , College of Physicians and Surgeons, , 630 West 168th Street, New York, NY 10032 , USA"},{"name":"Columbia University , College of Physicians and Surgeons, , 630 West 168th Street, New York, NY 10032 , USA"},{"name":"The Gertrude H. Sergievsky Center , College of Physicians and Surgeons, , 630 West 168th Street, New York, NY 10032 , USA"},{"name":"Columbia University , College of Physicians and Surgeons, , 630 West 168th Street, New York, NY 10032 , USA"},{"name":"Department of Neurology , College of Physicians and Surgeons, , 710 West 168th Street, New York, NY 10032 , USA"},{"name":"Columbia University and the New York Presbyterian Hospital , College of Physicians and Surgeons, , 710 West 168th Street, New York, NY 10032 , USA"}]},{"given":"Rosa","family":"Montesinos","sequence":"additional","affiliation":[{"name":"Unidad de diagn\u00f3stico de deterioro cognitivo y prevenci\u00f3n de demencia, Instituto Peruano de Neurociencias, Lima , Per\u00fa"}]},{"given":"Marcio","family":"Soto-A\u00f1ari","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencia Cognitiva , Arequipa , Per\u00fa"},{"name":"Laboratorio de Neurociencia, Universidad Cat\u00f3lica San Pablo , Arequipa , Per\u00fa"}]},{"given":"Nilton","family":"Custodio","sequence":"additional","affiliation":[{"name":"Unidad de diagn\u00f3stico de deterioro cognitivo y prevenci\u00f3n de demencia, Instituto Peruano de Neurociencias, Lima , Per\u00fa"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7075-8245","authenticated-orcid":false,"given":"Giuseppe","family":"Tosto","sequence":"additional","affiliation":[{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain , College of Physicians and Surgeons, , 630 West 168th Street, New York, NY 10032 , USA"},{"name":"Columbia University , College of Physicians and Surgeons, , 630 West 168th Street, New York, NY 10032 , USA"},{"name":"The Gertrude H. Sergievsky Center , College of Physicians and Surgeons, , 630 West 168th Street, New York, NY 10032 , USA"},{"name":"Columbia University , College of Physicians and Surgeons, , 630 West 168th Street, New York, NY 10032 , USA"},{"name":"Department of Neurology , College of Physicians and Surgeons, , 710 West 168th Street, New York, NY 10032 , USA"},{"name":"Columbia University and the New York Presbyterian Hospital , College of Physicians and Surgeons, , 710 West 168th Street, New York, NY 10032 , USA"}]}],"member":"286","published-online":{"date-parts":[[2023,11,30]]},"reference":[{"key":"2024031209435964400_ref1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: rising to the challenge of larger and richer 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