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Physical activity helps to counteract weight gain from obesity-causing gene variant

Study used meta-analyses that account for physical activity and identified 11 novel obesity variants



IMAGE: Physical activity can reduce the weight-gaining effects of the genetic variant that carries the greatest risk of obesity. view more

Credit: Ludo Rouchy, Flickr, CC BY

Physical activity can reduce the weight-gaining effects of the genetic variant that carries the greatest risk of obesity, report Mariaelisa Graff of the University of North Carolina at Chapel Hill, Tuomas Kilpeläinen of University of Copenhagen and colleagues April 27th, 2017 in PLOS Genetics.

With people consuming more calories and being less physically active, the world has witnessed an obesity epidemic, but not everyone is gaining weight. Previous studies suggest that a person's susceptibility to becoming obese can be reduced by physical activity. To see how physical activity and genetic variants related to obesity interact to affect weight gain, Graff and colleagues performed genome-wide interaction meta-analyses using more than 200,000 individuals. They categorized individuals as active or inactive, screened them for about 2.5 million genetic variants and correlated that data with physical indicators of obesity, including body mass index, waist circumference and waist-to-hip ratio. The study finds that physical activity can reduce the weight-gaining effects of the strongest known genetic risk factor for obesity, the FTO gene, by about 30%. Accounting for physical activity also enabled the researchers to identify 11 novel genetic variants linked to obesity, suggesting that physical activity and other relevant environmental factors should be considered when looking for novel genes.

The meta-analyses confirm previous findings that physical activity reduces the effect of the FTO gene, but the underlying cause of this interaction is still unknown. The scientists suspect that physical activity may affect other genes related to obesity, but to identify these smaller effects, researchers will require larger groups of subjects and highly precise measurements. From a practical standpoint, the findings suggest that physical activity is still vital, even when obesity appears to be predetermined in one's genes, and could be most beneficial for those who have the hardest time keeping weight off.

Mariaelisa Graff adds: "Moreover, our study revealed 11 completely new obesity genes, suggesting that in future studies, accounting for physical activity and other important lifestyle factors could boost the search new obesity genes. A weakness of our study was that the participants self-reported their physical activity habits rather than being surveyed objectively. To identify more genes whose effects are either dampened or amplified by physical activity, we need to carry out larger studies with more accurate measurement of physical levels."


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Citation: Graff M, Scott RA, Justice AE, Young KL, Feitosa MF, Barata L, et al. (2017) Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults. PLoS Genet 13(4): e1006528. doi:10.1371/journal.pgen.1006528

Funding: The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. Funding for this study was provided by the Aase and Ejner Danielsens Foundation; Academy of Finland (102318; 104781, 120315, 123885, 129619, 286284, 134309, 126925, 121584, 124282, 129378, 117787, 250207, 258753, 41071, 77299, 124243, 1114194, 24300796); Accare Center for Child and Adolescent Psychiatry; Action on Hearing Loss (G51); Agence Nationale de la Recherche; Agency for Health Care Policy Research (HS06516); Age UK Research into Ageing Fund; Åke Wiberg Foundation; ALF/LUA Research Grant in Gothenburg; ALFEDIAM; ALK-Abello´ A/S (Hørsholm, Denmark); American Heart Association (13POST16500011, 10SDG269004); Ardix Medical; Arthritis Research UK; Association Diabète Risque Vasculaire; AstraZeneca; Australian Associated Brewers; Australian National Health and Medical Research Council (241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498); Avera Research Institute; Bayer Diagnostics; Becton Dickinson; Biobanking and Biomolecular Resources Research Infrastructure (BBMRI -NL, 184.021.007); Biocentrum Helsinki; Boston Obesity Nutrition Research Center (DK46200); British Heart Foundation (RG/10/12/28456, SP/04/002); Canada Foundation for Innovation; Canadian Institutes of Health Research (FRN-CCT-83028); Cancer Research UK; Cardionics; Center for Medical Systems Biology; Center of Excellence in Complex Disease Genetics and SALVECenter of Excellence in Genomics (EXCEGEN); Chief Scientist Office of the Scottish Government; City of Kuopio; Cohortes Santé TGIR; Contrat de Projets État-Région; Croatian Science Foundation (8875); Danish Agency for Science, Technology and Innovation; Danish Council for Independent Research (DFF-1333-00124, DFF-1331-007308); Danish Diabetes Academy; Danish Medical Research Council; Department of Psychology and Education of the VU University Amsterdam; Diabetes Hilfs- und Forschungsfonds Deutschland; Dutch Brain Foundation; Dutch Ministry of Justice; Emil Aaltonen Foundation; Erasmus Medical Center; Erasmus University; Estonian Government (IUT20-60, IUT24-6); Estonian Ministry of Education and Research (3.2.0304.11-0312); European Commission (230374, 284167, 323195, 692145, FP7 EurHEALTHAgeing-277849, FP7 BBMRI-LPC 313010, nr 602633, HEALTH-F2-2008-201865-GEFOS, HEALTH-F4-2007-201413, FP6 LSHM-CT-2004-005272, FP5 QLG2-CT-2002-01254, FP6 LSHG-CT-2006-01947, FP7 HEALTH-F4-2007-201413, FP7 279143, FP7 201668, FP7 305739, FP6 LSHG-CT-2006-018947, HEALTH-F4-2007-201413, QLG1-CT-2001-01252); European Regional Development Fund; European Science Foundation (EuroSTRESS project FP-006, ESF, EU/QLRT-2001-01254); Faculty of Biology and Medicine of Lausanne; Federal Ministry of Education and Research (01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012, 03IS2061A); Federal State of Mecklenburg - West Pomerania; Fédération Française de Cardiologie; Finnish Cultural Foundation; Finnish Diabetes Association; Finnish Foundation of Cardiovascular Research; Finnish Heart Association; Food Standards Agency; Fondation de France; Fonds Santé; Genetic Association Information Network of the Foundation for the National Institutes of Health; German Diabetes Association; German Federal Ministry of Education and Research (BMBF, 01ER1206, 01ER1507); German Research Council (SFB-1052, SPP 1629 TO 718/2-1); GlaxoSmithKline; Göran Gustafssons Foundation; Göteborg Medical Society; Health and Safety Executive; Heart Foundation of Northern Sweden; Icelandic Heart Association; Icelandic Parliament; Imperial College Healthcare NHS Trust; INSERM, Réseaux en Santé Publique, Interactions entre les déterminants de la santé; Interreg IV Oberrhein Program (A28); Italian Ministry of Economy and Finance; Italian Ministry of Health (ICS110.1/RF97.71); John D and Catherine T MacArthur Foundation; Juho Vainio Foundation; King's College London; Kjell och Märta Beijers Foundation; Kuopio University Hospital; Kuopio, Tampere and Turku University Hospital Medical Funds (X51001); Leiden University Medical Center; Lilly; LMUinnovativ; Lundbeck Foundation; Lundberg Foundation; Medical Research Council of Canada; MEKOS Laboratories (Denmark); Merck Santé; Mid-Atlantic Nutrition Obesity Research Center (P30 DK72488); Ministère de l'Économie, de l'Innovation et des Exportations; Ministry for Health, Welfare and Sports of the Netherlands; Ministry of Cultural Affairs of the Federal State of Mecklenburg-West Pomerania; Ministry of Education and Culture of Finland (627;2004-2011); Ministry of Education, Culture and Science of the Netherlands; MRC Human Genetics Unit; MRC-GlaxoSmithKline Pilot Programme Grant (G0701863); Municipality of Rotterdam; Netherlands Bioinformatics Centre (2008.024); Netherlands Consortium for Healthy Aging (050-060-810); Netherlands Genomics Initiative; Netherlands Organisation for Health Research and Development (904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192); Netherlands Organisation for Health Research and Development (2010/31471/ZONMW); Netherlands Organisation for Scientific Research (10-000-1002, GB-MW 940-38-011, 100-001-004, 60-60600-97-118, 261-98-710, GB-MaGW 480-01-006, GB-MaGW 480-07-001, GB-MaGW 452-04-314, GB-MaGW 452-06-004, 175.010.2003.005, 175.010.2005.011, 481-08-013, 480-05-003, 911-03-012); Neuroscience Campus Amsterdam; NHS Foundation Trust; Novartis Pharmaceuticals; Novo Nordisk; Office National Interprofessionel des Vins; Paavo Nurmi Foundation; Påhlssons Foundation; Päivikki and Sakari Sohlberg Foundation; Pierre Fabre; Republic of Croatia Ministry of Science, Education and Sport (108-1080315-0302); Research Centre for Prevention and Health, the Capital Region for Denmark; Research Institute for Diseases in the Elderly (014-93-015, RIDE2); Roche; Russian Foundation for Basic Research (NWO-RFBR 047.017.043); Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06); Sanofi-Aventis; Scottish Executive Health Department (CZD/16/6); Siemens Healthcare; Social Insurance Institution of Finland (4/26/2010); Social Ministry of the Federal State of Mecklenburg-West Pomerania; Société Francophone du Diabète; State of Bavaria; Stroke Association; Swedish Diabetes Association; Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation (20140543); Swedish Research Council (2015-03657); Swedish Medical Research Council (K2007-66X-20270-01-3, 2011-2354); Swedish Society for Medical Research; Swiss National Science Foundation (33CSCO-122661, 33CS30-139468, 33CS30-148401); Tampere Tuberculosis Foundation; The Marcus Borgström Foundation; The Royal Society; The Wellcome Trust (084723/Z/08/Z, 088869/B/09/Z); Timber Merchant Vilhelm Bangs Foundation; Topcon; Torsten and Ragnar Söderberg's Foundation; UK Department of Health; UK Diabetes Association; UK Medical Research Council (MC_U106179471, G0500539, G0600705, G0601966, G0700931, G1002319, K013351, MC_UU_12019/1); UK National Institute for Health Research BioResource Clinical Research Facility and Biomedical Research Centre; UK National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre; UK National Institute for Health Research (RP-PG-0407-10371); Umeå University Career Development Award; United States - Israel Binational Science Foundation Grant (2011036); University Hospital Oulu (75617); University Medical Center Groningen; University of Tartu (SP1GVARENG); National Institutes of Health (AG13196, CA047988, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSC271201100004C, HHSN268200900041C, HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, HHSN268201500001I, HL36310, HG002651, HL034594, HL054457, HL054481, HL071981, HL084729, HL119443, HL126024, N01-AG12100, N01-AG12109, N01-HC25195, N01-HC55015, N01-HC55016, N01-HC55018, N01-HC55019, N01-HC55020, N01-HC55021, N01-HC55022, N01-HD95159, N01-HD95160, N01-HD95161, N01-HD95162, N01-HD95163, N01-HD95164, N01-HD95165, N01-HD95166, N01-HD95167, N01-HD95168, N01-HD95169, N01-HG65403, N02-HL64278, R01-HD057194, R01-HL087641, R01-HL59367, R01HL-086694, R01-HL088451, R24-HD050924, U01-HG-004402, HHSN268200625226C, UL1-RR025005, UL1-RR025005, UL1-TR-001079, UL1-TR-00040, AA07535, AA10248, AA11998, AA13320, AA13321, AA13326, AA14041, AA17688, DA12854, MH081802, MH66206, R01-D004215701A, R01-DK075787, R01-DK089256, R01-DK8925601, R01-HL088451, R01-HL117078, R01-DK062370, R01-DK072193, DK091718, DK100383, DK078616, 1Z01-HG000024, HL087660, HL100245, R01DK089256, 2T32HL007055-36, U01-HL072515-06, U01-HL84756, NIA-U01AG009740, RC2-AG036495, RC4-AG039029, R03 AG046389, 263-MA-410953, 263-MD-9164, 263-MD-821336, U01-HG004802, R37CA54281, R01CA63, P01CA33619, U01-CA136792, U01-CA98758, RC2-MH089951, MH085520, R01-D0042157-01A, MH081802, 1RC2-MH089951, 1RC2-MH089995, 1RL1MH08326801, U01-HG007376, 5R01-HL08767902, 5R01MH63706:02, HG004790, N01-WH22110, U01-HG007033, UM1CA182913, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221); USDA National Institute of Food and Agriculture (2007-35205-17883); Västra Götaland Foundation; Velux Foundation; Veterans Affairs (1 IK2 BX001823); Vleugels Foundation; VU University's Institute for Health and Care Research (EMGO+, HEALTH-F4-2007-201413) and Neuroscience Campus Amsterdam; Wellcome Trust (090532, 091551, 098051, 098381); Wissenschaftsoffensive TMO; and Yrjö Jahnsson Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

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