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

@article{Graff2017GenomewidePA,
  title={Genome-wide physical activity interactions in adiposity ― A meta-analysis of 200,452 adults},
  author={Mariaelisa Graff and Robert A Scott and Anne E. Justice and Kristin L. Young and Mary F. Feitosa and Llilda Barata and Thomas W. Winkler and Audrey Y. Chu and Anubha Mahajan and David Hadley and Luting Xue and Tsegaselassie Workalemahu and Nancy L. Heard-Costa and Marcel den Hoed and Tarunveer Singh Ahluwalia and Qibin Qi and Julius S Ngwa and Frida Renstr{\"o}m and Lydia Quaye and John D. Eicher and James E. Hayes and Marilyn C. Cornelis and Zolt{\'a}n Kutalik and Elise Lim and Jian’an Luan and Jennifer E. Huffman and Weihua Zhang and Wei Zhao and Paula J. Griffin and Toomas Haller and Shafqat Ahmad and Pedro Marques‐Vidal and Stephanie A. Bien and Loic Yengo and Alexander Teumer and Albert Vernon Smith and Meena Kumari and Marie Neergaard Harder and Johanne Marie Justesen and Marcus Edi Kleber and Mette Hollensted and Kurt K. Lohman and Natalia V. Rivera and John B. Whitfield and Jing Hua Zhao and Heather M. Stringham and Leo-Pekka Lyytik{\"a}inen and Charlotte Huppertz and Gonneke Willemsen and Wouter J. Peyrot and Ying Wu and Kati Kristiansson and Ayşe Demirkan and Myriam Fornage and Maija Hassinen and Lawrence F. Bielak and G. Cadby and Toshiko Tanaka and Reedik M{\"a}gi and Peter J. van der Most and Anne U. Jackson and Jennifer L. Bragg-Gresham and Veronique Vitart and Jonathan Marten and Pau Navarro and Claire Bellis and Dorota Pasko and {\AA}sa Johansson and S{\o}ren Snitker and Yuching Cheng and Joel Eriksson and Unhee Lim and Mette Aadahl and Linda S Adair and Najaf Amin and Beverley Balkau and Juha Auvinen and John P. Beilby and Richard N. Bergman and S. Bergmann and Alain G. Bertoni and John Blangero and Am{\'e}lie Bonnefond and Lori L Bonnycastle and Judith B. Borja and S{\o}ren Brage and Fabio Busonero and Steven Buyske and Harry Campbell and Peter S. Chines and Francis S. Collins and Tanguy Corre and George Davey Smith and Graciela E. Delgado and Nicole D Dueker and Marcus D{\"o}rr and Tapani Ebeling and Gudny Eiriksdottir and T{\~o}nu Esko and Jessica D Faul and Mao Fu and Kristine F{\ae}rch and Christian Gieger and Sven Gl{\"a}ser and Jian Gong and Penny Gordon-Larsen and Harald Grallert and Tanja B. Grammer and Niels Grarup and Gerard van Grootheest and Kennet Harald and Nicholas D. Hastie and Aki Samuli Havulinna and Dena G Hernandez and Lucia A. Hindorff and Lynne J. Hocking and Oddgeir L. Holmens and Christina Holzapfel and Jouke- Jan Hottenga and Jie Huang and Tao Huang and Jennie Hui and Cornelia Huth and Nina Hutri-K{\"a}h{\"o}nen and Alan L James and John-Olov Jansson and Min A. Jhun and Markus Juonala and Leena Kinnunen and Heikki A. Koistinen and Ivana Kol{\vc}i{\'c} and Pirjo Komulainen and Johanna Kuusisto and Kirsti Kval{\o}y and Mika K{\"a}h{\"o}nen and Timo A. Lakka and Lenore J. Launer and Benjamin C Lehne and Cecilia M. Lindgren and Mattias Lorentzon and Robert N. Luben and Michel Marre and Yuri Milaneschi and Keri L. Monda and Grant W. Montgomery and Marleen de Moor and Antonella Mulas and Martina M{\"u}ller-Nurasyid and Arthur William Musk and Reija M{\"a}nnikk{\"o} and Satu M{\"a}nnist{\"o} and Narisu Narisu and Matthias Nauck and Jennifer A. Nettleton and Ilja Maria Nolte and Albertine J. Oldehinkel and Matthias Olden and Ken K. Ong and Sandosh Padmanabhan and Lavinia Paternoster and Jeremiah Perez and Markus Perola and Annette Peters and Ulrike Peters and Patricia A. Peyser and Inga Prokopenko and Hannu Puolijoki and Olli T. Raitakari and Tuomo Rankinen and Laura J. Rasmussen-Torvik and Rajesh Rawal and Paul M. Ridker and Lynda M Rose and Igor Rudan and Cinzia Sarti and Mark A. Sarzynski and Kai Savonen and William R Scott and Serena Sanna and Alan R. Shuldiner and Stephen Sidney and G{\"u}nther Silbernagel and Blair H. Smith and Jennifer A. Smith and Harold Snieder and Alena Stan{\vc}{\'a}kov{\'a} and Barbara Sternfeld and Amy J. Swift and Tuija H. Tammelin and Sian-Tsung Tan and Barbara Thorand and Doroth{\'e}e Thuillier and Liesbeth Vandenput and Henrik Vestergaard and Jana V. van Vliet-Ostaptchouk and Marie-Claude Vohl and Uwe V{\"o}lker and G{\'e}rard Waeber and Mark Walker and Sarah H. Wild and Andrew Wong and Alan F. Wright and M. Carola Zillikens and Niha Zubair and Christopher A. Haiman and Loic LeMarchand and Ulf Gyllensten and Claes Ohlsson and Albert Hofman and Fernando Rivadeneira and Andr{\'e} G. Uitterlinden and Louis P{\'e}russe and James F. Wilson and Caroline Hayward and Ozren Pola{\vs}ek and Francesco Cucca and Kristian Hveem and Catharina A. Hartman and Anke Tönjes and Stefania Bandinelli and Lyle J. Palmer and Sharon L. R. Kardia and Rainer Rauramaa and Thorkild I. A. S{\o}rensen and Jaakko Tuomilehto and Veikko V Salomaa and Brenda W.J.H. Penninx and Eco J. C. de Geus and Dorret I. Boomsma and Terho Lehtim{\"a}ki and Massimo Mangino and Markku Laakso and Claude Bouchard and Nicholas G. Martin and Diana Kuh and Yongmei Liu and Allan Linneberg and Winfried M{\"a}rz and Konstantin Strauch and Mika Kivim{\"a}ki and Tamara B. Harris and Vilmundur G. Gudnason and Henry V{\"o}lzke and Lu Qi and Marjo-Riitta J{\"a}rvelin and John C Chambers and Jaspal S Kooner and Philippe Froguel and Charles Kooperberg and Peter Vollenweider and Göran Hallmans and Torben Hansen and Oluf Pedersen and Andres Metspalu and Nicholas J. Wareham and Claudia Langenberg and David R. Weir and David J. Porteous and Eric Boerwinkle and Daniel I. Chasman and Gonçalo R. Abecasis and In{\^e}s Barroso and Mark I. McCarthy and Timothy M. Frayling and Jeffrey R. O’Connell and Cornelia M. van Duijn and Michael Boehnke and Iris M. Heid and Karen L. Mohlke and David P. Strachan and Caroline S Fox and Ching‐Ti Liu and Joel N. Hirschhorn and Robert J. Klein and Andrew D. Johnson and Ingrid B. Borecki and Paul W. Franks and Kari E. North and L. Adrienne Cupples and Ruth J. F. Loos and Tuomas O. Kilpel{\"a}inen},
  journal={PLoS Genetics},
  year={2017},
  volume={13}
}
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… 

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References

SHOWING 1-10 OF 105 REFERENCES
Gene × Physical Activity Interactions in Obesity: Combined Analysis of 111,421 Individuals of European Ancestry
TLDR
A meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.
Physical activity attenuates the body mass index-increasing influence of genetic variation in the FTO gene.
TLDR
PA attenuates the effect of the FTO rs1121980 genotype on BMI and WC, showing that a genetic susceptibility to obesity induced by FTO variation can be overcome, at least in part, by adopting a physically active lifestyle.
New genetic loci link adipose and insulin biology to body fat distribution
TLDR
A genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
FTO genetic variants, dietary intake and body mass index: insights from 177,330 individuals.
TLDR
A positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake is suggested and insight is offered into potential link between FTO, dietaryprotein intake and adiposity.
Lifestyle Interaction With Fat Mass and Obesity-Associated (FTO) Genotype and Risk of Obesity in Apparently Healthy U.S. Women
TLDR
Healthier lifestyle patterns blunted but did not completely eliminate the associated genetic risk of FTO on obesity phenotypes, particularly among women who were both inactive and had high intake.
No Interactions Between Previously Associated 2-Hour Glucose Gene Variants and Physical Activity or BMI on 2-Hour Glucose Levels
TLDR
In this large study of gene–lifestyle interaction, no interactions between genetic and lifestyle factors are observed, and top loci from genome-wide association studies will not make the best candidates for the study of interactions.
Genetic studies of body mass index yield new insights for obesity biology
TLDR
A genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals provide strong support for a role of the central nervous system in obesity susceptibility.
Low Physical Activity Accentuates the Effect of the FTO rs9939609 Polymorphism on Body Fat Accumulation
TLDR
It is validated that variation in FTO is associated with type 2 diabetes when not adjusted for BMI and with an overall increase in body fat mass and low physical activity seems to accentuate the effect of FTO rs9939609 on body fat accumulation.
Fat and carbohydrate intake modify the association between genetic variation in the FTO genotype and obesity.
TLDR
The results indicate that high-fat diets and low physical activity levels may accentuate the susceptibility to obesity by the FTO variant.
A high intake of saturated fatty acids strengthens the association between the fat mass and obesity-associated gene and BMI.
TLDR
S FA intake modulates the association between FTO and BMI in American populations, and homozygous participants for the FTO-risk allele had a higher mean BMI than the other genotypes only when they had a high-SFA intake.
...
1
2
3
4
5
...