| Title: | Identification of novel and rare variants associated with handgrip strength using whole genome sequence data from the NHLBI Trans-Omics in Precision Medicine (TOPMed) Program |
| Journal: | PLOS ONE |
| Published: | 2 Jul 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34214102/ |
| DOI: | https://doi.org/10.1371/journal.pone.0253611 |
| URL: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0253611&type=printable |
| Citations: | 4 (3 in last 2 years) as of 8 Aug 2024 |
Publication 5167
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Abstract
Handgrip strength is a widely used measure of muscle strength and a predictor of a range of morbidities including cardiovascular diseases and all-cause mortality. Previous genome-wide association studies of handgrip strength have focused on common variants primarily in persons of European descent. We aimed to identify rare and ancestry-specific genetic variants associated with handgrip strength by conducting whole-genome sequence association analyses using 13,552 participants from six studies representing diverse population groups from the Trans-Omics in Precision Medicine (TOPMed) Program. By leveraging multiple handgrip strength measures performed in study participants over time, we increased our effective sample size by 7-12%. Single-variant analyses identified ten handgrip strength loci among African-Americans: four rare variants, five low-frequency variants, and one common variant. One significant and four suggestive genes were identified associated with handgrip strength when aggregating rare and functional variants; all associations were ancestry-specific. We additionally leveraged the different ancestries available in the UK Biobank to further explore the ancestry-specific association signals from the single-variant association analyses. In conclusion, our study identified 11 new loci associated with handgrip strength with rare and/or ancestry-specific genetic variations, highlighting the added value of whole-genome sequencing in diverse samples. Several of the associations identified using single-variant or aggregate analyses lie in genes with a function relevant to the brain or muscle or were reported to be associated with muscle or age-related traits. Further studies in samples with sequence data and diverse ancestries are needed to confirm these findings.</p>
28 Authors
- Chloé Sarnowski
- Han Chen
- Mary L. Biggs
- Sylvia Wassertheil-Smoller
- Jan Bressler
- Marguerite R. Irvin
- Kathleen A. Ryan
- David Karasik
- Donna K. Arnett
- L. Adrienne Cupples
- David W. Fardo
- Stephanie M. Gogarten
- Benjamin D. Heavner
- Deepti Jain
- Hyun Min Kang
- Charles Kooperberg
- Arch G. Mainous
- Braxton D. Mitchell
- Alanna C. Morrison
- Jeffrey R. O'Connell
- Bruce M. Psaty
- Kenneth Rice
- Albert V. Smith
- Ramachandran S. Vasan
- B. Gwen Windham
- Douglas P. Kiel
- Joanne M. Murabito
- Kathryn L. Lunetta
Enabling scientific discoveries that improve human health