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; Mette Aadahl; Kristine Færch; Niels Grarup; Henrik Vestergaard; Thorkild I.A. Sørensen; Allan Linneberg; Torben Hansen; Oluf Pedersen; Ruth J.F. Loos; Tuomas O. Kilpeläinen; CHARGE Consortium; EPIC-InterAct Consortium; PAGE 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, Mette Aadahl, Kristine Færch, Niels Grarup, Henrik Vestergaard, Thorkild I.A. Sørensen, Allan Linneberg, Torben Hansen, Oluf Pedersen, Ruth J.F. Loos, Tuomas O. Kilpeläinen, CHARGE Consortium, EPIC-InterAct Consortium, PAGE Consortium

^*Corresponding author for this work

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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
Journal	PLOS Genetics
Volume	13
Issue number	4
ISSN	1553-7390
DOIs	https://doi.org/10.1371/journal.pgen.1006528
Publication status	Published - 1 Apr 2017

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Genome-wide physical activity interactions in adiposity ― A meta-analysis of 200,452 adultsFinal published version, 2.53 MBLicence: CC0

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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., ... PAGE Consortium (2017). Genome-wide physical activity interactions in adiposity ― A meta-analysis of 200,452 adults. PLOS Genetics, 13(4), [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, Aadahl, M , Færch, K , Grarup, N , Vestergaard, H , Sørensen, TIA , Linneberg, A , Hansen, T , Pedersen, O, Loos, RJF, Kilpeläinen, TO, CHARGE Consortium, EPIC-InterAct Consortium & PAGE Consortium 2017, 'Genome-wide physical activity interactions in adiposity ― A meta-analysis of 200,452 adults', PLOS Genetics, vol. 13, no. 4, e1006528. 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.",

author = "Mariaelisa Graff and Scott, {Robert A.} and Justice, {Anne E.} and Young, {Kristin L.} and Feitosa, {Mary F.} and Llilda Barata and Winkler, {Thomas W.} and Chu, {Audrey Y.} and Anubha Mahajan and David Hadley and Luting Xue and Tsegaselassie Workalemahu and Heard-Costa, {Nancy L.} and {den Hoed}, Marcel and Ahluwalia, {Tarunveer S.} and Qibin Qi and Ngwa, {Julius S.} and Frida Renstr{\"o}m and Lydia Quaye and Eicher, {John D.} and Hayes, {James E.} and Marilyn Cornelis and Zoltan Kutalik and Elise Lim and Jian{\textquoteright}an Luan and Huffman, {Jennifer E.} and Weihua Zhang and Wei Zhao and Griffin, {Paula J.} and Toomas Haller and Shafqat Ahmad and Marques-Vidal, {Pedro M.} and Stephanie Bien and Loic Yengo and Alexander Teumer and Smith, {Albert Vernon} and Meena Kumari and Harder, {Marie Neergaard} and Justesen, {Johanne Marie} and Kleber, {Marcus E} and Mette Hollensted and Mette Aadahl and Kristine F{\ae}rch and Niels Grarup and Henrik Vestergaard and S{\o}rensen, {Thorkild I.A.} and Allan Linneberg and Torben Hansen and Oluf Pedersen and Loos, {Ruth J.F.} and Kilpel{\"a}inen, {Tuomas O.} and {CHARGE Consortium} and {EPIC-InterAct Consortium} and {PAGE Consortium}",

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doi = "10.1371/journal.pgen.1006528",

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T1 - Genome-wide physical activity interactions in adiposity ― A meta-analysis of 200,452 adults

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

AU - Ahluwalia, Tarunveer S.

AU - Qi, Qibin

AU - Ngwa, Julius S.

AU - Renström, Frida

AU - Quaye, Lydia

AU - Eicher, John D.

AU - Hayes, James E.

AU - Cornelis, Marilyn

AU - Kutalik, Zoltan

AU - Lim, Elise

AU - Luan, Jian’an

AU - Huffman, Jennifer E.

AU - Zhang, Weihua

AU - Zhao, Wei

AU - Griffin, Paula J.

AU - Haller, Toomas

AU - Ahmad, Shafqat

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 - Aadahl, Mette

AU - Færch, Kristine

AU - Grarup, Niels

AU - Vestergaard, Henrik

AU - Sørensen, Thorkild I.A.

AU - Linneberg, Allan

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Loos, Ruth J.F.

AU - Kilpeläinen, Tuomas O.

AU - CHARGE Consortium

AU - EPIC-InterAct Consortium

AU - PAGE Consortium

PY - 2017/4/1

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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.

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

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