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Whole genome sequencing analysis of body mass index identifies novel african ancestry-specific risk allele

Title: Whole genome sequencing analysis of body mass index identifies novel african ancestry-specific risk allele
Authors: Zhang; X; Brody; JA; Graff; M; Highland; HM; Chami; N; Xu; H; Wang; Z; Ferrier; K; Chittoor; G; Josyula; NS; Li; Allison; MA; Becker; DM; Bielak; LF; Bis; JC; Boorgula; MP; Bowden; DW; Broome; JG; Buth; EJ; Carlson; CS; Chang; KM; Chavan; S; Chiu; YF; Chuang; LM; Conomos; DeMeo; DL; Du; Duggirala; R; Eng; C; Fohner; AE; Freedman; BI; Garrett; ME; Guo; Haiman; Heavner; BD; Hidalgo; B; Hixson; JE; Ho; YL; Hobbs; Hu; D; Hui; Q; Hwu; CM; Jackson; RD; Jain; Kalyani; RR; Kardia; SLR; Kelly; TN; Lange; EM; LeNoir; Marchand; LL; McDonald; MN; McHugh; CP; Morrison; AC; Naseri; T; O'Connell; J; O'Donnell; CJ; Palmer; ND; Pankow; JS; Perry; Peters; U; Preuss; MH; Rao; DC; Regan; EA; Reupena; SM; Roden; Rodriguez-Santana; Sitlani; Smith; Tiwari; HK; Vasan; RS; Weeks; DE; Wessel; Wiggins; KL; Wilkens; LR; Wilson; PWF; Yanek; Yoneda; ZT; Zhao; W; Zöllner; Arnett; DK; Ashley-Koch; Barnes; KC; Blangero; Boerwinkle; E; Burchard; EG; Carson; AP; Chasman; DI; Chen; YI; Curran; Fornage; Gordeuk; VR; He; Heckbert; SR; Hou; L; Irvin; MR; Kooperberg; Minster; RL
Contributors: Institute of Population Health Sciences
Publication Year: 2023
Collection: National Health Research Institutes (NHRI): Institutional Repository / 國家衛生研究院機構典藏
Description: Obesity 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.
Document Type: article in journal/newspaper
File Description: 1092044 bytes; application/pdf
Language: English
Relation: medRxiv. 2023 Aug 22;Article in Press.; http://ir.nhri.org.tw/handle/3990099045/15385; http://ir.nhri.org.tw/bitstream/3990099045/15385/1/PUB37662265.pdf
DOI: 10.1101/2023.08.21.23293271
Availability: http://ir.nhri.org.tw/handle/3990099045/15385; https://doi.org/10.1101/2023.08.21.23293271; http://ir.nhri.org.tw/bitstream/3990099045/15385/1/PUB37662265.pdf
Accession Number: edsbas.48A72074
Database: BASE