Genome-wide Association Study of Liking for Several Types of Physical Activity in the UK Biobank and Two Replication Cohorts

Y.C. Klimentidis; M. Newell; M.D. Van Der Zee; V.L. Bland; S. May-Wilson; G. Arani; C. Menni; M. Mangino; A. Arora; D.A. Raichlen; G.E. Alexander; J.F. Wilson; D.I. Boomsma; J.-J. Hottenga; Eco .J.C. De Geus; N. Pirastu

doi:10.1249/MSS.0000000000002907

Genome-wide Association Study of Liking for Several Types of Physical Activity in the UK Biobank and Two Replication Cohorts

Y.C. Klimentidis, M. Newell, M.D. Van Der Zee, V.L. Bland, S. May-Wilson, G. Arani, C. Menni, M. Mangino, A. Arora, D.A. Raichlen, G.E. Alexander, J.F. Wilson, D.I. Boomsma, J.-J. Hottenga, Eco .J.C. De Geus, N. Pirastu

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Abstract

Introduction
A lack of physical activity (PA) is one of the most pressing health issues today. Our individual propensity for PA is influenced by genetic factors. Stated liking of different PA types may help capture additional and informative dimensions of PA behavior genetics.

Methods
In over 157,000 individuals from the UK Biobank, we performed genome-wide association studies of five items assessing the liking of different PA types, plus an additional derived trait of overall PA-liking. We attempted to replicate significant associations in the Netherlands Twin Register (NTR) and TwinsUK. Additionally, polygenic scores (PGS) were trained in the UK Biobank for each PA-liking item and for self-reported PA behavior, and tested for association with PA in the NTR.

Results
We identified a total of 19 unique significant loci across all five PA-liking items and the overall PA-liking trait, and these showed strong directional consistency in the replication cohorts. Four of these loci were previously identified for PA behavior, including CADM2, which was associated with three PA-liking items. The PA-liking items were genetically correlated with self-reported (rg = 0.38–0.80) and accelerometer (rg = 0.26–0.49) PA measures, and with a wide range of health-related traits. Each PA-liking PGS significantly predicted the same PA-liking item in NTR. The PGS of liking for going to the gym predicted PA behavior in the NTR (r2 = 0.40%) nearly as well as a PGS based on self-reported PA behavior (r2 = 0.42%). Combining the two PGS into a single model increased the r2 to 0.59%, suggesting that PA-liking captures distinct and relevant dimensions of PA behavior.

Conclusions
We have identified the first loci associated with PA-liking and extended our understanding of the genetic basis of PA behavior.

Original language	English
Pages (from-to)	1252-1260
Number of pages	9
Journal	Medicine and Science in Sports and Exercise
Volume	54
Issue number	8
Early online date	11 Mar 2022
DOIs	https://doi.org/10.1249/MSS.0000000000002907
Publication status	Published - Aug 2022

Funding

This research was conducted using the UK Biobank Resource under Application Number 15678 and 19655. The authors thank the funders, organizers, and participants of the UK Biobank, the Netherlands Twin Register, and TwinsUK. Y. C. K. acknowledges support from the NIH/NHLBI (R01-HL136528). J. F. W. acknowledges support from the MRC Human Genetics Unit quinquennial program grant \u201CQTL in Health and Disease\u201D (MC_UU_00007/10). TwinsUK receives funding from the Wellcome Trust (212904/Z/18/Z), Medical Research Council (AIMHY; MR/M016560/1), and European Union (H2020 contract #733100). TwinsUK and M. M. are supported by the National Institute for Health Research (NIHR)\u2013funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy\u2019s and St Thomas\u2019 NHS Foundation Trust in partnership with King\u2019s College London. C. M. is funded by the Chronic Disease Research Foundation and by the Medical Research Council (MRC)/British Heart Foundation Ancestry and Biological Informative Markers for Stratification of Hypertension (AIMHY; MR/M016560/1). G. E. A. acknowledges support from the National Institute on Aging, NIH (AG072980, AG067200, AG019610, AG064587), State of Arizona and Arizona Department of Health Services, and McKnight Brain Research Foundation. Phenotyping in NTR was funded by BBRMI-CP2011-38: Enrichment of NTR with information on dietary intake and aspects of eating behavior (PI: Boomsma and Feskens); genotyping in NTR was funded by multiple grants from the Netherlands Organization for Scientific Research (NWO) and The Netherlands Organization for Health Research and Development (ZonMW), the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL, 184.021.007 and 184.033.111), the European Community\u2019s Framework Programs (FP5-LIFE QUALITY-CT-2002-2006, FP7-HEALTH-F4-2007-2013, grant 01254: GenomEUtwin, grant 01413: ENGAGE); the European Research Council (ERC Starting 284167, ERC Consolidator 771057, ERC Advanced 230374), Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the National Institutes of Health (NIH, R01D0042157-01A1, MH081802, DA018673, R01 DK092127-04, Grand Opportunity grant 1RC2 MH089951), and the Avera Institute for Human Genetics, Sioux Falls, South Dakota (USA). The results of this study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by the American College of Sports Medicine. The authors have no relevant conflicts of interest to disclose.

Funders	Funder number
AIMHY	MR/M016560/1
BBMRI-NL	184.033.111, 184.021.007
Biobanking and Biomolecular Resources Research Infrastructure
European Community’s Framework Programs	FP5-LIFE QUALITY-CT-2002-2006
FP7-HEALTH-F4-2007-2013	01254, 01413
National Institutes of Health	1RC2 MH089951, R01 DK092127-04, DA018673, MH081802, R01D0042157-01A1
National Institute of Mental Health	U24 MH068457-06
National Institute on Aging	AG072980, AG067200, AG064587, AG019610
National Heart, Lung, and Blood Institute	MC_UU_00007/10, R01HL136528
Evelyn F. McKnight Brain Research Foundation	BBRMI-CP2011-38
Wellcome Trust	212904/Z/18/Z
Horizon 2020 Framework Programme	733100
Engineering Research Centers	230374, 284167
Medical Research Council
National Institute for Health and Care Research
British Heart Foundation
European Commission
European Research Council
ZonMw
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Avera Institute for Human Genetics

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10.1249/MSS.0000000000002907

GenomeWide Association Study of Liking for Several Types of Physical Activity in the UK Biobank and Two Replication CohortsFinal published version, 932 KBLicence: Article 25fa Dutch Copyright Act

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Klimentidis, Y. C., Newell, M., Van Der Zee, M. D., Bland, V. L., May-Wilson, S., Arani, G., Menni, C., Mangino, M., Arora, A., Raichlen, D. A., Alexander, G. E., Wilson, J. F., Boomsma, D. I., Hottenga, J.-J., De Geus, E. . J. C., & Pirastu, N. (2022). Genome-wide Association Study of Liking for Several Types of Physical Activity in the UK Biobank and Two Replication Cohorts. Medicine and Science in Sports and Exercise, 54(8), 1252-1260. https://doi.org/10.1249/MSS.0000000000002907

@article{04b2579b503c4dc29169a60703bab34d,

title = "Genome-wide Association Study of Liking for Several Types of Physical Activity in the UK Biobank and Two Replication Cohorts",

abstract = "Introduction A lack of physical activity (PA) is one of the most pressing health issues today. Our individual propensity for PA is influenced by genetic factors. Stated liking of different PA types may help capture additional and informative dimensions of PA behavior genetics.Methods In over 157,000 individuals from the UK Biobank, we performed genome-wide association studies of five items assessing the liking of different PA types, plus an additional derived trait of overall PA-liking. We attempted to replicate significant associations in the Netherlands Twin Register (NTR) and TwinsUK. Additionally, polygenic scores (PGS) were trained in the UK Biobank for each PA-liking item and for self-reported PA behavior, and tested for association with PA in the NTR.Results We identified a total of 19 unique significant loci across all five PA-liking items and the overall PA-liking trait, and these showed strong directional consistency in the replication cohorts. Four of these loci were previously identified for PA behavior, including CADM2, which was associated with three PA-liking items. The PA-liking items were genetically correlated with self-reported (rg = 0.38–0.80) and accelerometer (rg = 0.26–0.49) PA measures, and with a wide range of health-related traits. Each PA-liking PGS significantly predicted the same PA-liking item in NTR. The PGS of liking for going to the gym predicted PA behavior in the NTR (r2 = 0.40%) nearly as well as a PGS based on self-reported PA behavior (r2 = 0.42%). Combining the two PGS into a single model increased the r2 to 0.59%, suggesting that PA-liking captures distinct and relevant dimensions of PA behavior.Conclusions We have identified the first loci associated with PA-liking and extended our understanding of the genetic basis of PA behavior.",

author = "Y.C. Klimentidis and M. Newell and {Van Der Zee}, M.D. and V.L. Bland and S. May-Wilson and G. Arani and C. Menni and M. Mangino and A. Arora and D.A. Raichlen and G.E. Alexander and J.F. Wilson and D.I. Boomsma and J.-J. Hottenga and {De Geus}, {Eco .J.C.} and N. Pirastu",

year = "2022",

month = aug,

doi = "10.1249/MSS.0000000000002907",

language = "English",

volume = "54",

pages = "1252--1260",

journal = "Medicine and Science in Sports and Exercise",

issn = "0195-9131",

publisher = "Lippincott Williams and Wilkins",

number = "8",

}

Klimentidis, YC, Newell, M, Van Der Zee, MD, Bland, VL, May-Wilson, S, Arani, G, Menni, C, Mangino, M, Arora, A, Raichlen, DA, Alexander, GE, Wilson, JF, Boomsma, DI , Hottenga, J-J , De Geus, EJC & Pirastu, N 2022, 'Genome-wide Association Study of Liking for Several Types of Physical Activity in the UK Biobank and Two Replication Cohorts', Medicine and Science in Sports and Exercise, vol. 54, no. 8, pp. 1252-1260. https://doi.org/10.1249/MSS.0000000000002907

TY - JOUR

T1 - Genome-wide Association Study of Liking for Several Types of Physical Activity in the UK Biobank and Two Replication Cohorts

AU - Klimentidis, Y.C.

AU - Newell, M.

AU - Van Der Zee, M.D.

AU - Bland, V.L.

AU - May-Wilson, S.

AU - Arani, G.

AU - Menni, C.

AU - Mangino, M.

AU - Arora, A.

AU - Raichlen, D.A.

AU - Alexander, G.E.

AU - Wilson, J.F.

AU - Boomsma, D.I.

AU - Hottenga, J.-J.

AU - De Geus, Eco .J.C.

AU - Pirastu, N.

PY - 2022/8

Y1 - 2022/8

N2 - Introduction A lack of physical activity (PA) is one of the most pressing health issues today. Our individual propensity for PA is influenced by genetic factors. Stated liking of different PA types may help capture additional and informative dimensions of PA behavior genetics.Methods In over 157,000 individuals from the UK Biobank, we performed genome-wide association studies of five items assessing the liking of different PA types, plus an additional derived trait of overall PA-liking. We attempted to replicate significant associations in the Netherlands Twin Register (NTR) and TwinsUK. Additionally, polygenic scores (PGS) were trained in the UK Biobank for each PA-liking item and for self-reported PA behavior, and tested for association with PA in the NTR.Results We identified a total of 19 unique significant loci across all five PA-liking items and the overall PA-liking trait, and these showed strong directional consistency in the replication cohorts. Four of these loci were previously identified for PA behavior, including CADM2, which was associated with three PA-liking items. The PA-liking items were genetically correlated with self-reported (rg = 0.38–0.80) and accelerometer (rg = 0.26–0.49) PA measures, and with a wide range of health-related traits. Each PA-liking PGS significantly predicted the same PA-liking item in NTR. The PGS of liking for going to the gym predicted PA behavior in the NTR (r2 = 0.40%) nearly as well as a PGS based on self-reported PA behavior (r2 = 0.42%). Combining the two PGS into a single model increased the r2 to 0.59%, suggesting that PA-liking captures distinct and relevant dimensions of PA behavior.Conclusions We have identified the first loci associated with PA-liking and extended our understanding of the genetic basis of PA behavior.

AB - Introduction A lack of physical activity (PA) is one of the most pressing health issues today. Our individual propensity for PA is influenced by genetic factors. Stated liking of different PA types may help capture additional and informative dimensions of PA behavior genetics.Methods In over 157,000 individuals from the UK Biobank, we performed genome-wide association studies of five items assessing the liking of different PA types, plus an additional derived trait of overall PA-liking. We attempted to replicate significant associations in the Netherlands Twin Register (NTR) and TwinsUK. Additionally, polygenic scores (PGS) were trained in the UK Biobank for each PA-liking item and for self-reported PA behavior, and tested for association with PA in the NTR.Results We identified a total of 19 unique significant loci across all five PA-liking items and the overall PA-liking trait, and these showed strong directional consistency in the replication cohorts. Four of these loci were previously identified for PA behavior, including CADM2, which was associated with three PA-liking items. The PA-liking items were genetically correlated with self-reported (rg = 0.38–0.80) and accelerometer (rg = 0.26–0.49) PA measures, and with a wide range of health-related traits. Each PA-liking PGS significantly predicted the same PA-liking item in NTR. The PGS of liking for going to the gym predicted PA behavior in the NTR (r2 = 0.40%) nearly as well as a PGS based on self-reported PA behavior (r2 = 0.42%). Combining the two PGS into a single model increased the r2 to 0.59%, suggesting that PA-liking captures distinct and relevant dimensions of PA behavior.Conclusions We have identified the first loci associated with PA-liking and extended our understanding of the genetic basis of PA behavior.

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DO - 10.1249/MSS.0000000000002907

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JO - Medicine and Science in Sports and Exercise

JF - Medicine and Science in Sports and Exercise

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Genome-wide Association Study of Liking for Several Types of Physical Activity in the UK Biobank and Two Replication Cohorts

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