Advanced

Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women

Jones, Garan ; Karlsson, Magnus LU and Pilling, Luke C. (2021) In Nature Communications 12(1).
Abstract
Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1p = 4 × 10−17), arthritis (GDF5p = 4 × 10−13), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal... (More)
Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1p = 4 × 10−17), arthritis (GDF5p = 4 × 10−13), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing. © 2021, The Author(s). (Less)
Please use this url to cite or link to this publication:
author
; and
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
12
issue
1
article number
654
publisher
Nature Publishing Group
external identifiers
  • scopus:85100042471
  • pmid:33510174
ISSN
2041-1723
DOI
10.1038/s41467-021-20918-w
language
English
LU publication?
yes
id
db7fca04-91ef-4f7f-b4f2-1b38c8d03076
date added to LUP
2021-02-05 11:29:55
date last changed
2021-02-06 03:00:05
@article{db7fca04-91ef-4f7f-b4f2-1b38c8d03076,
  abstract     = {Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1p = 4 × 10−17), arthritis (GDF5p = 4 × 10−13), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing. © 2021, The Author(s).},
  author       = {Jones, Garan and Karlsson, Magnus and Pilling, Luke C.},
  issn         = {2041-1723},
  language     = {eng},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women},
  url          = {http://dx.doi.org/10.1038/s41467-021-20918-w},
  doi          = {10.1038/s41467-021-20918-w},
  volume       = {12},
  year         = {2021},
}