{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:00:56Z","timestamp":1791594056752,"version":"4.3.4"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"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":[[2018,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent technical and methodological advances have greatly enhanced genome-wide association studies (GWAS). The advent of low-cost, whole-genome sequencing facilitates high-resolution variant identification, and the development of linear mixed models (LMM) allows improved identification of putatively causal variants. While essential for correcting false positive associations due to sample relatedness and population stratification, LMMs have commonly been restricted to quantitative variables. However, phenotypic traits in association studies are often categorical, coded as binary case-control or ordered variables describing disease stages. To address these issues, we have devised a method for genomic association studies that implements a generalized LMM (GLMM) in a Bayesian framework, called Bayes-GLMM. Bayes-GLMM has four major features: (1) support of categorical, binary, and quantitative variables; (2) cohesive integration of previous GWAS results for related traits; (3) correction for sample relatedness by mixed modeling; and (4) model estimation by both Markov chain Monte Carlo sampling and maximal likelihood estimation. We applied Bayes-GLMM to the whole-genome sequencing cohort of the Alzheimer\u2019s Disease Sequencing Project. This study contains 570 individuals from 111 families, each with Alzheimer\u2019s disease diagnosed at one of four confidence levels. Using Bayes-GLMM we identified four variants in three loci significantly associated with Alzheimer\u2019s disease. Two variants, rs140233081 and rs149372995, lie between PRKAR1B and PDGFA. The coded proteins are localized to the glial-vascular unit, and PDGFA transcript levels are associated with Alzheimer\u2019s disease-related neuropathology. In summary, this work provides implementation of a flexible, generalized mixed-model approach in a Bayesian framework for association studies.<\/jats:p>","DOI":"10.1534\/genetics.117.300673","type":"journal-article","created":{"date-parts":[[2018,3,5]],"date-time":"2018-03-05T22:15:20Z","timestamp":1520288120000},"page":"51-64","source":"Crossref","is-referenced-by-count":18,"title":["A Bayesian Framework for Generalized Linear Mixed Modeling Identifies New Candidate Loci for Late-Onset Alzheimer\u2019s Disease"],"prefix":"10.1093","volume":"209","author":[{"given":"Xulong","family":"Wang","sequence":"first","affiliation":[{"name":"The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek M","family":"Philip","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guruprasad","family":"Ananda","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles C","family":"White","sequence":"additional","affiliation":[{"name":"Broad Institute, Cambridge, Massachusetts 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankit","family":"Malhotra","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J","family":"Michalski","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna R Murthy","family":"Karuturi","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumana R","family":"Chintalapudi","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey","family":"Acklin","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sasner","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Bennett","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, Illinois 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip L","family":"De Jager","sequence":"additional","affiliation":[{"name":"Broad Institute, Cambridge, Massachusetts 02142"},{"name":"Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, New York 10027"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth R","family":"Howell","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory W","family":"Carter","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,5,3]]},"reference":[{"key":"2022011723190677300_bib1","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation.","volume":"526","author":"Auton","year":"2015","journal-title":"Nature"},{"key":"2022011723190677300_bib2","doi-asserted-by":"crossref","first-page":"699","DOI":"10.3233\/JAD-2012-121060","article-title":"The imbalance of vascular molecules in Alzheimer\u2019s disease.","volume":"32","author":"Bell","year":"2012","journal-title":"J. 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