Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults

Mariaelisa Graff, Robert A Scott, Anne E Justice, Kristin L Young, Mary F Feitosa, Llilda Barata, Thomas W Winkler, Audrey Y Chu, Anubha Mahajan, David Hadley, Luting Xue, Tsegaselassie Workalemahu, Nancy L Heard-Costa, Marcel den Hoed, Tarunveer S Ahluwalia, Qibin Qi, Julius S Ngwa, Frida Renström, Lydia Quaye, John D Eicher & 31 others James E Hayes, Marilyn Cornelis, Zoltan Kutalik, Elise Lim, Jian'an Luan, Jennifer E Huffman, Weihua Zhang, Wei Zhao, Paula J Griffin, Toomas Haller, Shafqat Ahmad, Pedro M Marques-Vidal, Stephanie Bien, Loic Yengo, Alexander Teumer, Albert Vernon Smith, Meena Kumari, Marie Neergaard Harder, Johanne Marie Justesen, Marcus E Kleber, Mette Hollensted, Kurt Lohman, Natalia V Rivera, John B Whitfield, Jing Hua Zhao, Heather M Stringham, Leo-Pekka Lyytikäinen, Charlotte Huppertz, Gonneke Willemsen, Lynne J Hocking, CHARGE Consortium

Research output: Contribution to journalArticle

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Abstract

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.

Original languageEnglish
Article numbere1006528
Pages (from-to)1-26
Number of pages26
JournalPLoS Genetics
Volume13
Issue number4
DOIs
Publication statusPublished - 27 Apr 2017

Fingerprint

physical activity
Adiposity
meta-analysis
adiposity
Meta-Analysis
genome
Genome
Obesity
Waist-Hip Ratio
Genetic Association Studies
Waist Circumference
loci
obesity
Genes
waist
gene
waist circumference
hips
ancestry
environmental factor

Keywords

  • Adiposity
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Body Mass Index
  • Epigenomics
  • Exercise
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Obesity
  • Waist Circumference
  • Waist-Hip Ratio
  • Journal Article
  • Meta-Analysis

Cite this

Graff, M., Scott, R. A., Justice, A. E., Young, K. L., Feitosa, M. F., Barata, L., ... CHARGE Consortium (2017). Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults. PLoS Genetics, 13(4), 1-26. [e1006528]. https://doi.org/10.1371/journal.pgen.1006528

Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults. / Graff, Mariaelisa; Scott, Robert A; Justice, Anne E; Young, Kristin L; Feitosa, Mary F; Barata, Llilda; Winkler, Thomas W; Chu, Audrey Y; Mahajan, Anubha; Hadley, David; Xue, Luting; Workalemahu, Tsegaselassie; Heard-Costa, Nancy L; den Hoed, Marcel; Ahluwalia, Tarunveer S; Qi, Qibin; Ngwa, Julius S; Renström, Frida; Quaye, Lydia; Eicher, John D; Hayes, James E; Cornelis, Marilyn; Kutalik, Zoltan; Lim, Elise; Luan, Jian'an; Huffman, Jennifer E; Zhang, Weihua; Zhao, Wei; Griffin, Paula J; Haller, Toomas; Ahmad, Shafqat; Marques-Vidal, Pedro M; Bien, Stephanie; Yengo, Loic; Teumer, Alexander; Smith, Albert Vernon; Kumari, Meena; Harder, Marie Neergaard; Justesen, Johanne Marie; Kleber, Marcus E; Hollensted, Mette; Lohman, Kurt; Rivera, Natalia V; Whitfield, John B; Zhao, Jing Hua; Stringham, Heather M; Lyytikäinen, Leo-Pekka; Huppertz, Charlotte; Willemsen, Gonneke; Hocking, Lynne J; CHARGE Consortium.

In: PLoS Genetics, Vol. 13, No. 4, e1006528, 27.04.2017, p. 1-26.

Research output: Contribution to journalArticle

Graff, M, Scott, RA, Justice, AE, Young, KL, Feitosa, MF, Barata, L, Winkler, TW, Chu, AY, Mahajan, A, Hadley, D, Xue, L, Workalemahu, T, Heard-Costa, NL, den Hoed, M, Ahluwalia, TS, Qi, Q, Ngwa, JS, Renström, F, Quaye, L, Eicher, JD, Hayes, JE, Cornelis, M, Kutalik, Z, Lim, E, Luan, J, Huffman, JE, Zhang, W, Zhao, W, Griffin, PJ, Haller, T, Ahmad, S, Marques-Vidal, PM, Bien, S, Yengo, L, Teumer, A, Smith, AV, Kumari, M, Harder, MN, Justesen, JM, Kleber, ME, Hollensted, M, Lohman, K, Rivera, NV, Whitfield, JB, Zhao, JH, Stringham, HM, Lyytikäinen, L-P, Huppertz, C, Willemsen, G, Hocking, LJ & CHARGE Consortium 2017, 'Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults', PLoS Genetics, vol. 13, no. 4, e1006528, pp. 1-26. https://doi.org/10.1371/journal.pgen.1006528
Graff M, Scott RA, Justice AE, Young KL, Feitosa MF, Barata L et al. Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults. PLoS Genetics. 2017 Apr 27;13(4):1-26. e1006528. https://doi.org/10.1371/journal.pgen.1006528
Graff, Mariaelisa ; Scott, Robert A ; Justice, Anne E ; Young, Kristin L ; Feitosa, Mary F ; Barata, Llilda ; Winkler, Thomas W ; Chu, Audrey Y ; Mahajan, Anubha ; Hadley, David ; Xue, Luting ; Workalemahu, Tsegaselassie ; Heard-Costa, Nancy L ; den Hoed, Marcel ; Ahluwalia, Tarunveer S ; Qi, Qibin ; Ngwa, Julius S ; Renström, Frida ; Quaye, Lydia ; Eicher, John D ; Hayes, James E ; Cornelis, Marilyn ; Kutalik, Zoltan ; Lim, Elise ; Luan, Jian'an ; Huffman, Jennifer E ; Zhang, Weihua ; Zhao, Wei ; Griffin, Paula J ; Haller, Toomas ; Ahmad, Shafqat ; Marques-Vidal, Pedro M ; Bien, Stephanie ; Yengo, Loic ; Teumer, Alexander ; Smith, Albert Vernon ; Kumari, Meena ; Harder, Marie Neergaard ; Justesen, Johanne Marie ; Kleber, Marcus E ; Hollensted, Mette ; Lohman, Kurt ; Rivera, Natalia V ; Whitfield, John B ; Zhao, Jing Hua ; Stringham, Heather M ; Lyytikäinen, Leo-Pekka ; Huppertz, Charlotte ; Willemsen, Gonneke ; Hocking, Lynne J ; CHARGE Consortium. / Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults. In: PLoS Genetics. 2017 ; Vol. 13, No. 4. pp. 1-26.
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title = "Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults",
abstract = "Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23{\%} of participants were categorized as inactive and 77{\%} as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30{\%} in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.",
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AU - Graff, Mariaelisa

AU - Scott, Robert A

AU - Justice, Anne E

AU - Young, Kristin L

AU - Feitosa, Mary F

AU - Barata, Llilda

AU - Winkler, Thomas W

AU - Chu, Audrey Y

AU - Mahajan, Anubha

AU - Hadley, David

AU - Xue, Luting

AU - Workalemahu, Tsegaselassie

AU - Heard-Costa, Nancy L

AU - den Hoed, Marcel

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AU - Ahmad, Shafqat

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AU - Smith, Albert Vernon

AU - Kumari, Meena

AU - Harder, Marie Neergaard

AU - Justesen, Johanne Marie

AU - Kleber, Marcus E

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AU - Lohman, Kurt

AU - Rivera, Natalia V

AU - Whitfield, John B

AU - Zhao, Jing Hua

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AU - Huppertz, Charlotte

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AU - Hocking, Lynne J

AU - CHARGE Consortium

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PY - 2017/4/27

Y1 - 2017/4/27

N2 - Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.

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KW - Alpha-Ketoglutarate-Dependent Dioxygenase FTO

KW - Body Mass Index

KW - Epigenomics

KW - Exercise

KW - Female

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Male

KW - Obesity

KW - Waist Circumference

KW - Waist-Hip Ratio

KW - Journal Article

KW - Meta-Analysis

U2 - 10.1371/journal.pgen.1006528

DO - 10.1371/journal.pgen.1006528

M3 - Article

VL - 13

SP - 1

EP - 26

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 4

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