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; 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

doi:10.1371/journal.pgen.1006528

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 EicherJames 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

School of Medicine, Medical Sciences & Nutrition

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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 language	English
Article number	e1006528
Pages (from-to)	1-26
Number of pages	26
Journal	PLoS Genetics
Volume	13
Issue number	4
DOIs	https://doi.org/10.1371/journal.pgen.1006528
Publication status	Published - 27 Apr 2017

Bibliographical note

Data Availability: All genome-wide association meta-analysis results files are available at the GIANT Consortium website: www.broadinstitute.org/collaboration/giant.

https://figshare.com/articles/Genome-wide_physical_activity_interactions_in_adiposity_A_meta-analysis_of_200_452_adults/4925060

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.pgen.1006528Licence: CC0

Genome-wide physical activity interactions in adiposity ― A meta-analysis of 200,452 adults
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Graff, M., Scott, R. A., Justice, A. E., Young, K. L., Feitosa, M. F., Barata, L., Winkler, T. W., Chu, A. Y., Mahajan, A., Hadley, D., Xue, L., Workalemahu, T., Heard-Costa, N. L., den Hoed, M., Ahluwalia, T. S., Qi, Q., Ngwa, J. S., Renström, F., Quaye, L., ... CHARGE Consortium (2017). Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults. PLoS Genetics, 13(4), 1-26. Article e1006528. https://doi.org/10.1371/journal.pgen.1006528

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

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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 - 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

AU - Ahluwalia, Tarunveer S

AU - Qi, Qibin

AU - Ngwa, Julius S

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AU - Marques-Vidal, Pedro M

AU - Bien, Stephanie

AU - Yengo, Loic

AU - Teumer, Alexander

AU - Smith, Albert Vernon

AU - Kumari, Meena

AU - Harder, Marie Neergaard

AU - Justesen, Johanne Marie

AU - Kleber, Marcus E

AU - Hollensted, Mette

AU - Lohman, Kurt

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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

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ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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