Whole Genome Sequencing Analysis of Body Mass Index Identifies Novel African Ancestry-Specific Risk Allele

dc.contributor.authorZhang, Xinruo
dc.contributor.authorBrody, Jennifer A.
dc.contributor.authorGraff, Mariaelisa
dc.contributor.authorHighland, Heather M.
dc.contributor.authorChami, Nathalie
dc.contributor.authorXu, Hanfei
dc.contributor.authorWang, Zhe
dc.contributor.authorFerrier, Kendra
dc.contributor.authorChittoor, Geetha
dc.contributor.authorJosyula, Navya S.
dc.contributor.authorLi, Xihao
dc.contributor.authorLi, Zilin
dc.contributor.authorAllison, Matthew A.
dc.contributor.authorBecker, Diane M.
dc.contributor.authorBielak, Lawrence F.
dc.contributor.authorBis, Joshua C.
dc.contributor.authorBoorgula, Meher Preethi
dc.contributor.authorBowden, Donald W.
dc.contributor.authorBroome, Jai G.
dc.contributor.authorButh, Erin J.
dc.contributor.authorCarlson, Christopher S.
dc.contributor.authorChang, Kyong-Mi
dc.contributor.authorChavan, Sameer
dc.contributor.authorChiu, Yen-Feng
dc.contributor.authorChuang, Lee-Ming
dc.contributor.authorConomos, Matthew P.
dc.contributor.authorDeMeo, Dawn L.
dc.contributor.authorDu, Margaret
dc.contributor.authorDuggirala, Ravindranath
dc.contributor.authorEng, Celeste
dc.contributor.authorFohner, Alison E.
dc.contributor.authorFreedman, Barry I.
dc.contributor.authorGarrett, Melanie E.
dc.contributor.authorGuo, Xiuqing
dc.contributor.authorHaiman, Chris
dc.contributor.authorHeavner, Benjamin D.
dc.contributor.authorHidalgo, Bertha
dc.contributor.authorHixson, James E.
dc.contributor.authorHo, Yuk-Lam
dc.contributor.authorHobbs, Brian D.
dc.contributor.authorHu, Donglei
dc.contributor.authorHui, Qin
dc.contributor.authorHwu, Chii-Min
dc.contributor.authorJackson, Rebecca D.
dc.contributor.authorJain, Deepti
dc.contributor.authorKalyani, Rita R.
dc.contributor.authorKardia, Sharon L. R.
dc.contributor.authorKelly, Tanika N.
dc.contributor.authorLange, Ethan M.
dc.contributor.authorLeNoir, Michael
dc.contributor.authorLi, Changwei
dc.contributor.authorMarchand, Loic Le
dc.contributor.authorMcDonald, Merry-Lynn N.
dc.contributor.authorMcHugh, Caitlin P.
dc.contributor.authorMorrison, Alanna C.
dc.contributor.authorNaseri, Take
dc.contributor.authorNHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
dc.contributor.authorO'Connell, Jeffrey
dc.contributor.authorO'Donnell, Christopher J.
dc.contributor.authorPalmer, Nicholette D.
dc.contributor.authorPankow, James S.
dc.contributor.authorPerry, James A.
dc.contributor.authorPeters, Ulrike
dc.contributor.authorPreuss, Michael H.
dc.contributor.authorRao, D. C.
dc.contributor.authorRegan, Elizabeth A.
dc.contributor.authorReupena, Sefuiva M.
dc.contributor.authorRoden, Dan M.
dc.contributor.authorRodriguez-Santana, Jose
dc.contributor.authorSitlani, Colleen M.
dc.contributor.authorSmith, Jennifer A.
dc.contributor.authorTiwari, Hemant K.
dc.contributor.authorVasan, Ramachandran S.
dc.contributor.authorWang, Zeyuan
dc.contributor.authorWeeks, Daniel E.
dc.contributor.authorWessel, Jennifer
dc.contributor.authorWiggins, Kerri L.
dc.contributor.authorWilkens, Lynne R.
dc.contributor.authorWilson, Peter W. F.
dc.contributor.authorYanek, Lisa R.
dc.contributor.authorYoneda, Zachary T.
dc.contributor.authorZhao, Wei
dc.contributor.authorZöllner, Sebastian
dc.contributor.authorArnett, Donna K.
dc.contributor.authorAshley-Koch, Allison E.
dc.contributor.authorBarnes, Kathleen C.
dc.contributor.authorBlangero, John
dc.contributor.authorBoerwinkle, Eric
dc.contributor.authorBurchard, Esteban G.
dc.contributor.authorCarson, April P.
dc.contributor.authorChasman, Daniel I.
dc.contributor.authorChen, Yii-Der Ida
dc.contributor.authorCurran, Joanne E.
dc.contributor.authorFornage, Myriam
dc.contributor.authorGordeuk, Victor R.
dc.contributor.authorHe, Jiang
dc.contributor.authorHeckbert, Susan R.
dc.contributor.authorHou, Lifang
dc.contributor.authorIrvin, Marguerite R.
dc.contributor.authorKooperberg, Charles
dc.contributor.authorMinster, Ryan L.
dc.contributor.authorMitchell, Braxton D.
dc.contributor.authorNouraie, Mehdi
dc.contributor.authorPsaty, Bruce M.
dc.contributor.authorRaffield, Laura M.
dc.contributor.authorReiner, Alexander P.
dc.contributor.authorRich, Stephen S.
dc.contributor.authorRotter, Jerome I.
dc.contributor.authorShoemaker, M. Benjamin
dc.contributor.authorSmith, Nicholas L.
dc.contributor.authorTaylor, Kent D.
dc.contributor.authorTelen, Marilyn J.
dc.contributor.authorWeiss, Scott T.
dc.contributor.authorZhang, Yingze
dc.contributor.authorHeard-Costa, Nancy
dc.contributor.authorSun, Yan V.
dc.contributor.authorLin, Xihong
dc.contributor.authorCupples, L. Adrienne
dc.contributor.authorLange, Leslie A.
dc.contributor.authorLiu, Ching-Ti
dc.contributor.authorLoos, Ruth J. F.
dc.contributor.authorNorth, Kari E.
dc.contributor.authorJustice, Anne E.
dc.contributor.departmentBiostatistics and Health Data Science, School of Medicine
dc.date.accessioned2024-03-15T16:17:42Z
dc.date.available2024-03-15T16:17:42Z
dc.date.issued2023-08-22
dc.description.abstractObesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51% were of non-European population groups. We discovered 18 BMI-associated signals (P < 5 × 10−9). Notably, we identified and replicated a novel low frequency single nucleotide polymorphism (SNP) in MTMR3 that was common in individuals of African descent. Using a diverse study population, we further identified two novel secondary signals in known BMI loci and pinpointed two likely causal variants in the POC5 and DMD loci. Our work demonstrates the benefits of combining WGS and diverse cohorts in expanding current catalog of variants and genes confer risk for obesity, bringing us one step closer to personalized medicine.
dc.eprint.versionPre-Print
dc.identifier.citationZhang X, Brody JA, Graff M, et al. WHOLE GENOME SEQUENCING ANALYSIS OF BODY MASS INDEX IDENTIFIES NOVEL AFRICAN ANCESTRY-SPECIFIC RISK ALLELE. Preprint. medRxiv. 2023;2023.08.21.23293271. Published 2023 Aug 22. doi:10.1101/2023.08.21.23293271
dc.identifier.urihttps://hdl.handle.net/1805/39289
dc.language.isoen_US
dc.publishermedRxiv
dc.relation.isversionof10.1101/2023.08.21.23293271
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourcePMC
dc.subjectObesity
dc.subjectMortality
dc.subjectBody mass index (BMI)
dc.subjectPersonalized medicine
dc.titleWhole Genome Sequencing Analysis of Body Mass Index Identifies Novel African Ancestry-Specific Risk Allele
dc.typeArticle
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