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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.

SUBMITTER: Graff M

PROVIDER: S-EPMC5407576 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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

Graff Mariaelisa M Scott Robert A RA Justice Anne E AE Young Kristin L KL Feitosa Mary F MF Barata Llilda L Winkler Thomas W TW Chu Audrey Y AY Mahajan Anubha A Hadley David D Xue Luting L Workalemahu Tsegaselassie T Heard-Costa Nancy L NL den Hoed Marcel M Ahluwalia Tarunveer S TS Qi Qibin Q Ngwa Julius S JS Renström Frida F Quaye Lydia L Eicher John D JD Hayes James E JE Cornelis Marilyn M Kutalik Zoltan Z Lim Elise E Luan Jian'an J Huffman Jennifer E JE Zhang Weihua W Zhao Wei W Griffin Paula J PJ Haller Toomas T Ahmad Shafqat S Marques-Vidal Pedro M PM Bien Stephanie S Yengo Loic L Teumer Alexander A Smith Albert Vernon AV Kumari Meena M Harder Marie Neergaard MN Justesen Johanne Marie JM Kleber Marcus E ME Hollensted Mette M Lohman Kurt K Rivera Natalia V NV Whitfield John B JB Zhao Jing Hua JH Stringham Heather M HM Lyytikäinen Leo-Pekka LP Huppertz Charlotte C Willemsen Gonneke G Peyrot Wouter J WJ Wu Ying Y Kristiansson Kati K Demirkan Ayse A Fornage Myriam M Hassinen Maija M Bielak Lawrence F LF Cadby Gemma G Tanaka Toshiko T Mägi Reedik R van der Most Peter J PJ Jackson Anne U AU Bragg-Gresham Jennifer L JL Vitart Veronique V Marten Jonathan J Navarro Pau P Bellis Claire C Pasko Dorota D Johansson Åsa Å Snitker Søren S Cheng Yu-Ching YC Eriksson Joel J Lim Unhee U Aadahl Mette M Adair Linda S LS Amin Najaf N Balkau Beverley B Auvinen Juha J Beilby John J Bergman Richard N RN Bergmann Sven S Bertoni Alain G AG Blangero John J Bonnefond Amélie A Bonnycastle Lori L LL Borja Judith B JB Brage Søren S Busonero Fabio F Buyske Steve S Campbell Harry H Chines Peter S PS Collins Francis S FS Corre Tanguy T Smith George Davey GD Delgado Graciela E GE Dueker Nicole N Dörr Marcus M Ebeling Tapani T Eiriksdottir Gudny G Esko Tõnu T Faul Jessica D JD Fu Mao M Færch Kristine K Gieger Christian C Gläser Sven S Gong Jian J Gordon-Larsen Penny P Grallert Harald H Grammer Tanja B TB Grarup Niels N van Grootheest Gerard G Harald Kennet K Hastie Nicholas D ND Havulinna Aki S AS Hernandez Dena D Hindorff Lucia L Hocking Lynne J LJ Holmens Oddgeir L OL Holzapfel Christina C Hottenga Jouke Jan JJ Huang Jie J Huang Tao T Hui Jennie J Huth Cornelia C Hutri-Kähönen Nina N James Alan L AL Jansson John-Olov JO Jhun Min A MA Juonala Markus M Kinnunen Leena L Koistinen Heikki A HA Kolcic Ivana I Komulainen Pirjo P Kuusisto Johanna J Kvaløy Kirsti K Kähönen Mika M Lakka Timo A TA Launer Lenore J LJ Lehne Benjamin B Lindgren Cecilia M CM Lorentzon Mattias M Luben Robert R Marre Michel M Milaneschi Yuri Y Monda Keri L KL Montgomery Grant W GW De Moor Marleen H M MHM Mulas Antonella A Müller-Nurasyid Martina M Musk A W AW Männikkö Reija R Männistö Satu S Narisu Narisu N Nauck Matthias M Nettleton Jennifer A JA Nolte Ilja M IM Oldehinkel Albertine J AJ Olden Matthias M Ong Ken K KK Padmanabhan Sandosh S Paternoster Lavinia L Perez Jeremiah J Perola Markus M Peters Annette A Peters Ulrike U Peyser Patricia A PA Prokopenko Inga I Puolijoki Hannu H Raitakari Olli T OT Rankinen Tuomo T Rasmussen-Torvik Laura J LJ Rawal Rajesh R Ridker Paul M PM Rose Lynda M LM Rudan Igor I Sarti Cinzia C Sarzynski Mark A MA Savonen Kai K Scott William R WR Sanna Serena S Shuldiner Alan R AR Sidney Steve S Silbernagel Günther G Smith Blair H BH Smith Jennifer A JA Snieder Harold H Stančáková Alena A Sternfeld Barbara B Swift Amy J AJ Tammelin Tuija T Tan Sian-Tsung ST Thorand Barbara B Thuillier Dorothée D Vandenput Liesbeth L Vestergaard Henrik H van Vliet-Ostaptchouk Jana V JV Vohl Marie-Claude MC Völker Uwe U Waeber Gérard G Walker Mark M Wild Sarah S Wong Andrew A Wright Alan F AF Zillikens M Carola MC Zubair Niha N Haiman Christopher A CA Lemarchand Loic L Gyllensten Ulf U Ohlsson Claes C Hofman Albert A Rivadeneira Fernando F Uitterlinden André G AG Pérusse Louis L Wilson James F JF Hayward Caroline C Polasek Ozren O Cucca Francesco F Hveem Kristian K Hartman Catharina A CA Tönjes Anke A Bandinelli Stefania S Palmer Lyle J LJ Kardia Sharon L R SLR Rauramaa Rainer R Sørensen Thorkild I A TIA Tuomilehto Jaakko J Salomaa Veikko V Penninx Brenda W J H BWJH de Geus Eco J C EJC Boomsma Dorret I DI Lehtimäki Terho T Mangino Massimo M Laakso Markku M Bouchard Claude C Martin Nicholas G NG Kuh Diana D Liu Yongmei Y Linneberg Allan A März Winfried W Strauch Konstantin K Kivimäki Mika M Harris Tamara B TB Gudnason Vilmundur V Völzke Henry H Qi Lu L Järvelin Marjo-Riitta MR Chambers John C JC Kooner Jaspal S JS Froguel Philippe P Kooperberg Charles C Vollenweider Peter P Hallmans Göran G Hansen Torben T Pedersen Oluf O Metspalu Andres A Wareham Nicholas J NJ Langenberg Claudia C Weir David R DR Porteous David J DJ Boerwinkle Eric E Chasman Daniel I DI Abecasis Gonçalo R GR Barroso Inês I McCarthy Mark I MI Frayling Timothy M TM O'Connell Jeffrey R JR van Duijn Cornelia M CM Boehnke Michael M Heid Iris M IM Mohlke Karen L KL Strachan David P DP Fox Caroline S CS Liu Ching-Ti CT Hirschhorn Joel N JN Klein Robert J RJ Johnson Andrew D AD Borecki Ingrid B IB Franks Paul W PW North Kari E KE Cupples L Adrienne LA Loos Ruth J F RJF Kilpeläinen Tuomas O TO

PLoS genetics 20170427 4

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% ...[more]

PMID: 28448500

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Project description:The prevalence of adiposity is increasing among adult women. Although emerging evidence suggest that all patterns of heightened physical activity (PA) are important to benefit adiposity, the relationship between objectively assessed intensities of PA and adiposity in women has not yet been assessed. Therefore, this systematic review and meta-analysis aims to qualitatively synthesize and quantitatively assess the evidence for any relationship between objectively measured PA and a wide range of adiposity indicators to guide PA prescription in adult women. Four databases (PubMed, Web of Science, Scopus, and the Cochrane library) were searched for eligible studies. 35 studies were included (25 observational and 10 interventional studies), with a total of 9,176 women from 20 countries included. The overall pooled correlation for random effects model (n = 1 intervention and n = 15 cross-sectional studies) revealed that the total volume of physical activity (TPA) was moderately associated with percentage body fat (%BF) (r = -0.59; 95% CI: -1.11, -0.24; p = 0.003). There was a weak but significant association between MVPA with body mass index (BMI), waist circumference (WC), and visceral adiposity. Daily steps were significantly associated with BMI, %BF, WC, and fat mass, with the strongest association with %BF (r = -0.41; 95% CI: -0.66, -0.19; p < 0.001). Walking programs resulting in increasing daily steps only had a significant effect on WC (SMD = -0.35; 95% CI: -0.65, -0.05; p = 0.02). Overall, objectively determined PA in terms of steps, TPA and MVPA were favorably associated with adiposity outcomes. The improvement in adiposity can be achieved by simply accumulating more PA than previously and adiposity is more likely to be benefited by PA performed at higher intensity. Nonetheless, these results should be interpreted with caution as there were a small number of studies included in the meta-analysis and the majority of studies included utilized cross-sectional designs.

Project description:Background:The body of evidence related to the effect of physical activity monitor-based interventions has grown over the recent years. However, the effect of physical activity monitor-based interventions in older adults remains unclear and should be systematically reviewed. Objective:The objective of this systematic review was to estimate the effect of physical activity monitor-based interventions on physical activity behavior in participants aged 65 and above. Subsequently we explored the effect on body mass index, physical capacity, and health-related quality of life and finally the impact of patient- and intervention characteristics. Methods:Searches in MEDLINE, EMBASE, SPORTDiscus, CINAHL, and CENTRAL were performed on April 26, 2018. No publication date filters were applied. References of eligible studies were scrutinized and relevant journals were hand-searched. Randomized controlled trials and randomized cross-over trials investigating the effect of a physical activity monitor-based intervention on physical activity were included. Studies were included if the mean age of the participants was above 65?years, and participants could walk independently with or without walking aids. The Cochrane handbook was used as a template for extracting data and the RoB 2.0 tool was used to assess risk of bias. Random-effects meta-analysis using Hedges g, were used to pool the study results. The main outcome of this study was physical activity. Results:Twenty-one studies with 2783 participants were included. The median participant age in the studies was 70.5?years, the median percentage of male participants was 42%, and the median baseline daily step count was 5268. Physical activity monitor-based interventions had a moderate effect (SMD?=?0.54, 95% CI: 0.34 to 0.73) compared to control interventions, corresponding to an average increase of 1297 steps per day in the intervention groups. No impact of patient and intervention characteristics on the effect estimates were found. Short conclusion:Low quality of evidence was found for a moderate effect of physical activity monitor-based interventions on physical activity compared with control interventions. More studies with higher research methodology standards are required. PROSPERO registration:CRD42018083648.

Project description:BackgroundSeveral non-synonymous single-nucleotide polymorphisms (nsSNPs) have been shown to be associated with obesity. Little is known about their associations and interactions with physical activity (PA) in relation to adiposity parameters among adolescents in Malaysia.MethodsWe examined whether (a) PA and (b) selected nsSNPs are associated with adiposity parameters and whether PA interacts with these nsSNPs on these outcomes in adolescents from the Malaysian Health and Adolescents Longitudinal Research Team study (n = 1,151). Body mass indices, waist-hip ratio, and percentage body fat (% BF) were obtained. PA was assessed using Physical Activity Questionnaire for Older Children (PAQ-C). Five nsSNPs were included: beta-3 adrenergic receptor (ADRB3) rs4994, FABP2 rs1799883, GHRL rs696217, MC3R rs3827103, and vitamin D receptor rs2228570, individually and as combined genetic risk score (GRS). Associations and interactions between nsSNPs and PAQ-C scores were examined using generalized linear model.ResultsPAQ-C scores were associated with % BF (β = -0.44 [95% confidence interval -0.72, -0.16], p = 0.002). The CC genotype of ADRB3 rs4994 (β = -0.16 [-0.28, -0.05], corrected p = 0.01) and AA genotype of MC3R rs3827103 (β = -0.06 [-0.12, -0.00], p = 0.02) were significantly associated with % BF compared to TT and GG genotypes, respectively. Significant interactions with PA were found between ADRB3 rs4994 (β = -0.05 [-0.10, -0.01], p = 0.02) and combined GRS (β = -0.03 [-0.04, -0.01], p = 0.01) for % BF.ConclusionHigher PA score was associated with reduced % BF in Malaysian adolescents. Of the nsSNPs, ADRB3 rs4994 and MC3R rs3827103 were associated with % BF. Significant interactions with PA were found for ADRB3 rs4994 and combined GRS on % BF but not on measurements of weight or circumferences. Targeting body fat represent prospects for molecular studies and lifestyle intervention in this population.

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

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

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