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

Publication ,  Journal Article
Zhang, X; Brody, JA; Graff, M; Highland, HM; Chami, N; Xu, H; Wang, Z; Ferrier, KR; Chittoor, G; Josyula, NS; Meyer, M; Gupta, S; Li, X ...
Published in: Nat Commun
April 11, 2025

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), including two secondary signals. 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.

Duke Scholars

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

April 11, 2025

Volume

16

Issue

1

Start / End Page

3470

Location

England

Related Subject Headings

  • Whole Genome Sequencing
  • Population Groups
  • Polymorphism, Single Nucleotide
  • Obesity
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
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Zhang, X., Brody, J. A., Graff, M., Highland, H. M., Chami, N., Xu, H., … Justice, A. E. (2025). Whole genome sequencing analysis of body mass index identifies novel African ancestry-specific risk allele. Nat Commun, 16(1), 3470. https://doi.org/10.1038/s41467-025-58420-2
Zhang, Xinruo, Jennifer A. Brody, Mariaelisa Graff, Heather M. Highland, Nathalie Chami, Hanfei Xu, Zhe Wang, et al. “Whole genome sequencing analysis of body mass index identifies novel African ancestry-specific risk allele.Nat Commun 16, no. 1 (April 11, 2025): 3470. https://doi.org/10.1038/s41467-025-58420-2.
Zhang X, Brody JA, Graff M, Highland HM, Chami N, Xu H, et al. Whole genome sequencing analysis of body mass index identifies novel African ancestry-specific risk allele. Nat Commun. 2025 Apr 11;16(1):3470.
Zhang, Xinruo, et al. “Whole genome sequencing analysis of body mass index identifies novel African ancestry-specific risk allele.Nat Commun, vol. 16, no. 1, Apr. 2025, p. 3470. Pubmed, doi:10.1038/s41467-025-58420-2.
Zhang X, Brody JA, Graff M, Highland HM, Chami N, Xu H, Wang Z, Ferrier KR, Chittoor G, Josyula NS, Meyer M, Gupta S, Li X, Li Z, Allison MA, Becker DM, Bielak LF, Bis JC, Boorgula MP, Bowden DW, Broome JG, Buth EJ, Carlson CS, Chang K-M, Chavan S, Chiu Y-F, Chuang L-M, Conomos MP, DeMeo DL, Du M, Duggirala R, Eng C, Fohner AE, Freedman BI, Garrett ME, Guo X, Haiman C, Heavner BD, Hidalgo B, Hixson JE, Ho Y-L, Hobbs BD, Hu D, Hui Q, Hwu C-M, Jackson RD, Jain D, Kalyani RR, Kardia SLR, Kelly TN, Lange EM, LeNoir M, Li C, Le Marchand L, McDonald M-LN, McHugh CP, Morrison AC, Naseri T, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, O’Connell J, O’Donnell CJ, Palmer ND, Pankow JS, Perry JA, Peters U, Preuss MH, Rao DC, Regan EA, Reupena SM, Roden DM, Rodriguez-Santana J, Sitlani CM, Smith JA, Tiwari HK, Vasan RS, Weeks DE, Wessel J, Wiggins KL, Wilkens LR, Wilson PWF, Yanek LR, Yoneda ZT, Zhao W, Zöllner S, Arnett DK, Ashley-Koch AE, Barnes KC, Blangero J, Boerwinkle E, Burchard EG, Carson AP, Chasman DI, Ida Chen Y-D, Curran JE, Fornage M, Gordeuk VR, He J, Heckbert SR, Hou L, Irvin MR, Kooperberg C, Minster RL, Mitchell BD, Nouraie M, Psaty BM, Raffield LM, Reiner AP, Rich SS, Rotter JI, Benjamin Shoemaker M, Smith NL, Taylor KD, Telen MJ, Weiss ST, Zhang Y, Heard-Costa N, Sun YV, Lin X, Cupples LA, Lange LA, Liu C-T, Loos RJF, North KE, Justice AE. Whole genome sequencing analysis of body mass index identifies novel African ancestry-specific risk allele. Nat Commun. 2025 Apr 11;16(1):3470.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

April 11, 2025

Volume

16

Issue

1

Start / End Page

3470

Location

England

Related Subject Headings

  • Whole Genome Sequencing
  • Population Groups
  • Polymorphism, Single Nucleotide
  • Obesity
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Female