| Authors: |
Zhang, X.; Brody, J. A.; Graff, M.; Highland, H. M.; Chami, N.; Xu, H.; Wang, Z.; Ferrier, K. R.; Chittoor, G.; Josyula, N. S.; Meyer, M.; Gupta, S.; Li, X.; Li, Z.; Allison, M. A.; Becker, D. M.; Bielak, L. F.; Bis, J. C.; Boorgula, M. P.; Bowden, D. W.; Broome, J. G.; Buth, E. J.; Carlson, C. S.; Chang, K. M.; Chavan, S.; Chiu, Y. F.; Chuang, L. M.; Conomos, M. P.; DeMeo, D. L.; Du, M.; Duggirala, R.; Eng, C.; Fohner, A. E.; Freedman, B. I.; Garrett, M. E.; Guo, X.; Haiman, C.; Heavner, B. D.; Hidalgo, B.; Hixson, J. E.; Ho, Y. L.; Hobbs, B. D.; Hu, D.; Hui, Q.; Hwu, C. M.; Jackson, R. D.; Jain, D.; Kalyani, R. R.; Kardia, S. L. R.; Kelly, T. N.; Lange, E. M.; LeNoir, M.; Li, C.; Le Marchand, L.; McDonald, M. L. N.; McHugh, C. P.; Morrison, A. C.; Naseri, T.; O'Connell, J.; O'Donnell, C. J.; Palmer, N. D.; Pankow, J. S.; Perry, J. A.; Peters, U.; Preuss, M. H.; Rao, D. C.; Regan, E. A.; Reupena, S. M.; Roden, D. M.; Rodriguez-Santana, J.; Sitlani, C. M.; Smith, J. A.; Tiwari, H. K.; Vasan, R. S.; Wang, Z.; Weeks, D. E.; Wessel, J.; Wiggins, K. L.; Wilkens, L. R.; Wilson, P. W. F.; Yanek, L. R.; Yoneda, Z. T.; Zhao, W.; Zöllner, S.; Arnett, D. K.; Ashley-Koch, A. E.; Barnes, K. C.; Blangero, J.; Boerwinkle, E.; Burchard, E. G.; Carson, A. P.; Chasman, D. I.; Ida Chen, Y. D.; Curran, J. E.; Fornage, M.; Gordeuk, V. R.; He, J.; Heckbert, S. R.; Hou, L.; Irvin, M. R.; Kooperberg, C.; Minster, R. L.; Mitchell, B. D.; Nouraie, M.; Psaty, B. M.; Raffield, L. M.; Reiner, A. P.; Rich, S. S.; Rotter, J. I.; Benjamin Shoemaker, M.; Smith, N. L.; Taylor, K. D.; Telen, M. J.; Weiss, S. T.; Zhang, Y.; Heard-Costa, N.; Sun, Y. V.; Lin, X.; Cupples, L. A.; Lange, L. A.; Liu, C. T.; Loos, R. J. F.; North, K. E.; Justice, A. E. |
| Article Title: |
Whole genome sequencing analysis of body mass index identifies novel African ancestry-specific risk allele |
| Abstract: |
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. © 2025. The Author(s). |
| Keywords: |
adult; middle aged; single nucleotide polymorphism; genetics; polymorphism, single nucleotide; allele; genetic predisposition to disease; alleles; genome-wide association study; obesity; body mass; body mass index; genetic predisposition; ethnology; humans; human; male; female; whole genome sequencing; black person; black people
|
| Journal Title: |
Nature Communications
|
| Volume: |
16 |
| ISSN: |
2041-1723 |
| Publisher: |
Nature Publishing Group
|
| Date Published: |
2025-04-11 |
| Start Page: |
3470 |
| Language: |
English |
| DOI: |
10.1038/s41467-025-58420-2
|
| PUBMED: |
40216759
|
| PROVIDER: |
scopus
|
| PMCID: |
PMC11992084
|
| DOI/URL: |
|
| Notes: |
The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF -- Source: Scopus |
