Details

Autor(en) / Beteiligte

• Chen, Han
• Biggs, Mary L
• Psaty, Bruce M
• Mainous, Arch G
• Ryan, Kathleen A
• Irvin, Marguerite R
• Wassertheil-Smoller, Sylvia
• Bressler, Jan
• Vasan, Ramachandran S
• Smith, Albert V
• Heavner, Benjamin D
• Fardo, David W
• Morrison, Alanna C
• Cupples, L. Adrienne
• Jain, Deepti
• Mitchell, Braxton D
• Sarnowski, Chloé
• O'Connell, Jeffrey R
• Murabito, Joanne M
• Rice, Kenneth
• Arnett, Donna K
• Windham, B. Gwen
• Kang, Hyun Min
• Lunetta, Kathryn L
• Karasik, David
• Kooperberg, Charles
• Gogarten, Stephanie M
• Kiel, Douglas P

Titel

Identification of novel and rare variants associated with handgrip strength using whole genome sequence data from the NHLBI Trans-Omics in Precision Medicine

Ist Teil von

• PloS one, 2021-07, Vol.16 (7), p.e0253611

Ort / Verlag

Public Library of Science

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.