Show simple item record

dc.contributor.authorSomineni, Hari K
dc.contributor.authorNagpal, Sini
dc.contributor.authorVenkateswaran, Suresh
dc.contributor.authorCutler, David J
dc.contributor.authorOkou, David T
dc.contributor.authorHaritunians, Talin
dc.contributor.authorSimpson, Claire L
dc.contributor.authorBegum, Ferdouse
dc.contributor.authorDatta, Lisa W
dc.contributor.authorQuiros, Antonio J
dc.contributor.authorSeminerio, Jenifer
dc.contributor.authorMengesha, Emebet
dc.contributor.authorAlexander, Jonathan S
dc.contributor.authorBaldassano, Robert N
dc.contributor.authorDudley-Brown, Sharon
dc.contributor.authorCross, Raymond K
dc.contributor.authorDassopoulos, Themistocles
dc.contributor.authorDenson, Lee A
dc.contributor.authorDhere, Tanvi A
dc.contributor.authorIskandar, Heba
dc.contributor.authorDryden, Gerald W
dc.contributor.authorHou, Jason K
dc.contributor.authorHussain, Sunny Z
dc.contributor.authorHyams, Jeffrey S
dc.contributor.authorIsaacs, Kim L
dc.contributor.authorKader, Howard
dc.contributor.authorKappelman, Michael D
dc.contributor.authorKatz, Jeffry
dc.contributor.authorKellermayer, Richard
dc.contributor.authorKuemmerle, John F
dc.contributor.authorLazarev, Mark
dc.contributor.authorLi, Ellen
dc.contributor.authorMannon, Peter
dc.contributor.authorMoulton, Dedrick E
dc.contributor.authorNewberry, Rodney D
dc.contributor.authorPatel, Ashish S
dc.contributor.authorPekow, Joel
dc.contributor.authorSaeed, Shehzad A
dc.contributor.authorValentine, John F
dc.contributor.authorWang, Ming-Hsi
dc.contributor.authorMcCauley, Jacob L
dc.contributor.authorAbreu, Maria T
dc.contributor.authorJester, Traci
dc.contributor.authorMolle-Rios, Zarela
dc.contributor.authorPalle, Sirish
dc.contributor.authorScherl, Ellen J
dc.contributor.authorKwon, John
dc.contributor.authorRioux, John D
dc.contributor.authorDuerr, Richard H
dc.contributor.authorSilverberg, Mark S
dc.contributor.authorZwick, Michael E
dc.contributor.authorStevens, Christine
dc.contributor.authorDaly, Mark J
dc.contributor.authorCho, Judy H
dc.contributor.authorGibson, Greg
dc.contributor.authorMcGovern, Dermot P B
dc.contributor.authorBrant, Steven R
dc.contributor.authorKugathasan, Subra
dc.date.accessioned2021-03-12T21:31:05Z
dc.date.available2021-03-12T21:31:05Z
dc.date.issued2021-02-17
dc.identifier.urihttp://hdl.handle.net/10713/14925
dc.description.abstractWhether or not populations diverge with respect to the genetic contribution to risk of specific complex diseases is relevant to understanding the evolution of susceptibility and origins of health disparities. Here, we describe a large-scale whole-genome sequencing study of inflammatory bowel disease encompassing 1,774 affected individuals and 1,644 healthy control Americans with African ancestry (African Americans). Although no new loci for inflammatory bowel disease are discovered at genome-wide significance levels, we identify numerous instances of differential effect sizes in combination with divergent allele frequencies. For example, the major effect at PTGER4 fine maps to a single credible interval of 22 SNPs corresponding to one of four independent associations at the locus in European ancestry individuals but with an elevated odds ratio for Crohn disease in African Americans. A rare variant aggregate analysis implicates Ca2+-binding neuro-immunomodulator CALB2 in ulcerative colitis. Highly significant overall overlap of common variant risk for inflammatory bowel disease susceptibility between individuals with African and European ancestries was observed, with 41 of 241 previously known lead variants replicated and overall correlations in effect sizes of 0.68 for combined inflammatory bowel disease. Nevertheless, subtle differences influence the performance of polygenic risk scores, and we show that ancestry-appropriate weights significantly improve polygenic prediction in the highest percentiles of risk. The median amount of variance explained per locus remains the same in African and European cohorts, providing evidence for compensation of effect sizes as allele frequencies diverge, as expected under a highly polygenic model of disease.en_US
dc.description.urihttps://doi.org/10.1016/j.ajhg.2021.02.001en_US
dc.language.isoenen_US
dc.publisherElsevier Inc.en_US
dc.relation.ispartofAmerican Journal of Human Geneticsen_US
dc.rightsCopyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.en_US
dc.subjectCALB2en_US
dc.subjectPTGER4en_US
dc.subjectdifferential genetic architectureen_US
dc.subjectpolygenic risk scoresen_US
dc.subjectrare variantsen_US
dc.subjecttrans-ethnic comparative analysisen_US
dc.subjectunderstudied populationsen_US
dc.subjectwhole-genome sequencing of African Americansen_US
dc.titleWhole-genome sequencing of African Americans implicates differential genetic architecture in inflammatory bowel disease.en_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.ajhg.2021.02.001
dc.identifier.pmid33600772
dc.source.volume108
dc.source.issue3
dc.source.beginpage431
dc.source.endpage445
dc.source.countryUnited States


Files in this item

Thumbnail
Name:
Publisher version

This item appears in the following Collection(s)

Show simple item record