Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness

Sara M Willems; Daniel J. Wright; Felix R Day; Katerina Trajanoska; Peter K. Joshi; John A. Morris; Amy M. Matteini; Fleur C. Garton; Niels Grarup; Nikolay Oskolkov; Anbupalam Thalamuthu; Massimo Mangino; Jun Liu; Ayse Demirkan; Monkol Lek; Liwen Xu; Guan Wang; Christopher Oldmeadow; Kyle J Gaulton; Luca A. Lotta; Eri Miyamoto-Mikami; Manuel A. Rivas; Tom White; Po Ru Loh; Mette Aadahl; Najaf Amin; John R Attia; Krista Austin; Beben Benyamin; Søren Brage; Yu Ching Cheng; Paweł Ciȩszczyk; Wim Derave; Karl Fredrik Eriksson; Nir Eynon; Allan Linneberg; Alejandro Lucia; Myosotis Massidda; Braxton D. Mitchell; Motohiko Miyachi; Haruka Murakami; Sandosh Padmanabhan; Ashutosh Pandey; Ioannis Papadimitriou; Deepak K. Rajpal; Craig Sale; Cecilia M. Lindgren; Paul W. Franks; Ola Hansson; Thorvaldur Ingvarsson; GEFOS Anytype of Fracture Consortium

doi:10.1038/ncomms16015

Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness

Sara M Willems, Daniel J. Wright, Felix R Day, Katerina Trajanoska, Peter K. Joshi, John A. Morris, Amy M. Matteini, Fleur C. Garton, Niels Grarup, Nikolay Oskolkov, Anbupalam Thalamuthu, Massimo Mangino, Jun Liu, Ayse Demirkan, Monkol Lek, Liwen Xu, Guan Wang, Christopher Oldmeadow, Kyle J Gaulton, Luca A. LottaEri Miyamoto-Mikami, Manuel A. Rivas, Tom White, Po Ru Loh, Mette Aadahl, Najaf Amin, John R Attia, Krista Austin, Beben Benyamin, Søren Brage, Yu Ching Cheng, Paweł Ciȩszczyk, Wim Derave, Karl Fredrik Eriksson, Nir Eynon, Allan Linneberg, Alejandro Lucia, Myosotis Massidda, Braxton D. Mitchell, Motohiko Miyachi, Haruka Murakami, Sandosh Padmanabhan, Ashutosh Pandey, Ioannis Papadimitriou, Deepak K. Rajpal, Craig Sale, Cecilia M. Lindgren, Paul W. Franks, Ola Hansson, Thorvaldur Ingvarsson, GEFOS Anytype of Fracture Consortium

Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

Sammanfattning

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 genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.

Originalspråk	engelska
Artikelnummer	16015
Tidskrift	Nature Communications
Volym	8
DOI	https://doi.org/10.1038/ncomms16015
Status	Published - 2017 juli 12

Ämnesklassifikation (UKÄ)

Medicinsk genetik
Fysiologi

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10.1038/ncomms16015

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Willems, S. M., Wright, D. J., Day, F. R., Trajanoska, K., Joshi, P. K., Morris, J. A., Matteini, A. M., Garton, F. C., Grarup, N., Oskolkov, N., Thalamuthu, A., Mangino, M., Liu, J., Demirkan, A., Lek, M., Xu, L., Wang, G., Oldmeadow, C., Gaulton, K. J., ... GEFOS Anytype of Fracture Consortium (2017). Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness. Nature Communications, 8, [16015]. https://doi.org/10.1038/ncomms16015

@article{d51024e06b804e15a8907e4e996f6d3f,

title = "Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness",

abstract = "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 genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.",

author = "Willems, {Sara M} and Wright, {Daniel J.} and Day, {Felix R} and Katerina Trajanoska and Joshi, {Peter K.} and Morris, {John A.} and Matteini, {Amy M.} and Garton, {Fleur C.} and Niels Grarup and Nikolay Oskolkov and Anbupalam Thalamuthu and Massimo Mangino and Jun Liu and Ayse Demirkan and Monkol Lek and Liwen Xu and Guan Wang and Christopher Oldmeadow and Gaulton, {Kyle J} and Lotta, {Luca A.} and Eri Miyamoto-Mikami and Rivas, {Manuel A.} and Tom White and Loh, {Po Ru} and Mette Aadahl and Najaf Amin and Attia, {John R} and Krista Austin and Beben Benyamin and S{\o}ren Brage and Cheng, {Yu Ching} and Pawe{\l} Ciȩszczyk and Wim Derave and Eriksson, {Karl Fredrik} and Nir Eynon and Allan Linneberg and Alejandro Lucia and Myosotis Massidda and Mitchell, {Braxton D.} and Motohiko Miyachi and Haruka Murakami and Sandosh Padmanabhan and Ashutosh Pandey and Ioannis Papadimitriou and Rajpal, {Deepak K.} and Craig Sale and Lindgren, {Cecilia M.} and Franks, {Paul W.} and Ola Hansson and Thorvaldur Ingvarsson and {GEFOS Anytype of Fracture Consortium}",

year = "2017",

month = jul,

day = "12",

doi = "10.1038/ncomms16015",

language = "English",

volume = "8",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Willems, SM, Wright, DJ, Day, FR, 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, LA, Miyamoto-Mikami, E, Rivas, MA, White, T, Loh, PR, Aadahl, M, Amin, N, Attia, JR, Austin, K, Benyamin, B, Brage, S, Cheng, YC, Ciȩszczyk, P, Derave, W, Eriksson, KF, Eynon, N, Linneberg, A, Lucia, A, Massidda, M, Mitchell, BD, Miyachi, M, Murakami, H, Padmanabhan, S, Pandey, A, Papadimitriou, I, Rajpal, DK, Sale, C, Lindgren, CM, Franks, PW , Hansson, O, Ingvarsson, T & GEFOS Anytype of Fracture Consortium 2017, 'Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness', Nature Communications, vol. 8, 16015. https://doi.org/10.1038/ncomms16015

TY - JOUR

T1 - Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness

AU - Willems, Sara M

AU - Wright, Daniel J.

AU - Day, Felix R

AU - Trajanoska, Katerina

AU - Joshi, Peter K.

AU - Morris, John A.

AU - Matteini, Amy M.

AU - Garton, Fleur C.

AU - Grarup, Niels

AU - Oskolkov, Nikolay

AU - Thalamuthu, Anbupalam

AU - Mangino, Massimo

AU - Liu, Jun

AU - Demirkan, Ayse

AU - Lek, Monkol

AU - Xu, Liwen

AU - Wang, Guan

AU - Oldmeadow, Christopher

AU - Gaulton, Kyle J

AU - Lotta, Luca A.

AU - Miyamoto-Mikami, Eri

AU - Rivas, Manuel A.

AU - White, Tom

AU - Loh, Po Ru

AU - Aadahl, Mette

AU - Amin, Najaf

AU - Attia, John R

AU - Austin, Krista

AU - Benyamin, Beben

AU - Brage, Søren

AU - Cheng, Yu Ching

AU - Ciȩszczyk, Paweł

AU - Derave, Wim

AU - Eriksson, Karl Fredrik

AU - Eynon, Nir

AU - Linneberg, Allan

AU - Lucia, Alejandro

AU - Massidda, Myosotis

AU - Mitchell, Braxton D.

AU - Miyachi, Motohiko

AU - Murakami, Haruka

AU - Padmanabhan, Sandosh

AU - Pandey, Ashutosh

AU - Papadimitriou, Ioannis

AU - Rajpal, Deepak K.

AU - Sale, Craig

AU - Lindgren, Cecilia M.

AU - Franks, Paul W.

AU - Hansson, Ola

AU - Ingvarsson, Thorvaldur

AU - GEFOS Anytype of Fracture Consortium

PY - 2017/7/12

Y1 - 2017/7/12

N2 - 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 genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.

AB - 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 genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.

U2 - 10.1038/ncomms16015

DO - 10.1038/ncomms16015

M3 - Article

C2 - 29313844

AN - SCOPUS:85024482942

VL - 8

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 16015

ER -

Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness

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