Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness
- Willems, SM
- Wright, Daniel
- Day, Felix
- Trajanoska, K
- Joshi, PK
- Morris, JA
- Matteini, AM
- Garton, FC
- Grarup, N
- Oskolkov, N
- Thalamuthu, A
- Mangino, M
- Liu, J
- Demirkan, A
- Lek, M
- Xu, L
- Wang, G
- Oldmeadow, C
- Gaulton, KJ
- Lotta, Luca
- Miyamoto-Mikami, E
- Rivas, MA
- White, Thomas
- Loh, P-R
- Aadahl, M
- Amin, N
- Attia, JR
- Austin, K
- Benyamin, B
- Brage, Soren
- Cheng, Y-C
- Cięszczyk, P
- Derave, W
- Eriksson, K-F
- Eynon, N
- Linneberg, A
- Lucia, A
- Massidda, M
- Mitchell, BD
- Miyachi, M
- Murakami, H
- Padmanabhan, S
- Pandey, A
- Papadimitriou, I
- Rajpal, DK
- Sale, C
- Schnurr, TM
- Sessa, F
- Shrine, N
- Tobin, MD
- Varley, I
- Wain, LV
- Wray, NR
- Lindgren, CM
- MacArthur, DG
- Waterworth, D
- McCarthy, MI
- Pedersen, O
- Khaw, Kay-Tee
- Kiel, DP
- Pitsiladis, Y
- Fuku, N
- Franks, PW
- North, KN
- van Duijn, CM
- Mather, KA
- Hansen, T
- Hansson, O
- Spector, T
- Murabito, JM
- Richards, JB
- Rivadeneira, F
- Langenberg, Claudia
- Perry, John
- Wareham, Nicholas
- Scott, Robert
DOIAbstract
Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10−8) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher ...
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