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Author Bjornland, T.; Langaas, M.; Grill, V.; Mostad, I.L. url  doi
  Title Assessing gene-environment interaction effects of FTO, MC4R and lifestyle factors on obesity using an extreme phenotype sampling design: Results from the HUNT study Type Journal Article
  Year 2017 Publication PloS one Abbreviated Journal PLoS One  
  Volume 12 Issue (up) 4 Pages e0175071  
  Keywords Alpha-Ketoglutarate-Dependent Dioxygenase FTO/*genetics; Body Mass Index; *Gene-Environment Interaction; Humans; *Life Style; Obesity/*genetics; *Phenotype; Receptor, Melanocortin, Type 4/*genetics; Waist-Hip Ratio  
  Abstract BACKGROUND: Our aim was to assess the influence of age, gender and lifestyle factors on the effect of the obesity-promoting alleles of FTO and MCR4. METHODS: The HUNT study comprises health information on the population of Nord-Trondelag county, Norway. Extreme phenotype participants (gender-wise lower and upper quartiles of waist-hip-ratio and BMI >/= 35 kg/m2) in the third survey, HUNT3 (2006-08), were genotyped for the single-nucleotide polymorphisms rs9939609 (FTO) and rs17782313 (MC4R); 25686 participants were successfully genotyped. Extreme sampling was chosen to increase power to detect genetic and gene-environment effects on waist-hip-ratio and BMI. Statistical inference was based on linear regression models and a missing-covariate likelihood approach for the extreme phenotype sampling design. Environmental factors were physical activity, diet (artificially sweetened beverages) and smoking. Longitudinal analysis was performed using material from HUNT2 (1995-97). RESULTS: Cross-sectional and longitudinal genetic effects indicated stronger genetic associations with obesity in young than in old, as well as differences between women and men. We observed larger genetic effects among physically inactive compared to active individuals. This interaction was age-dependent and seen mainly in 20-40 year olds. We observed a greater FTO effect among men with a regular intake of artificially sweetened beverages, compared to non-drinkers. Interaction analysis of smoking was mainly inconclusive. CONCLUSIONS: In a large all-adult and area-based population survey the effects of obesity-promoting minor-alleles of FTO and MCR4, and interactions with life style factors are age- and gender-related. These findings appear relevant when designing individualized treatment for and prophylaxis against obesity.  
  Address Department of Clinical Nutrition and Speech-Language Therapy, Clinic of Clinical Services, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1932-6203 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28384342; PMCID:PMC5383228 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1884  
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Author 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.; Renstrom, F.; Quaye, L.; Eicher, J.D.; Hayes, J.E.; Cornelis, M.; Kutalik, Z.; Lim, E.; Luan, J.'an; Huffman, J.E.; Zhang, W.; Zhao, W.; Griffin, P.J.; Haller, T.; Ahmad, S.; Marques-Vidal, P.M.; Bien, S.; Yengo, L.; Teumer, A.; Smith, A.V.; Kumari, M.; Harder, M.N.; Justesen, J.M.; Kleber, M.E.; Hollensted, M.; Lohman, K.; Rivera, N.V.; Whitfield, J.B.; Zhao, J.H.; Stringham, H.M.; Lyytikainen, L.-P.; Huppertz, C.; Willemsen, G.; Peyrot, W.J.; Wu, Y.; Kristiansson, K.; Demirkan, A.; Fornage, M.; Hassinen, M.; Bielak, L.F.; Cadby, G.; Tanaka, T.; Magi, R.; van der Most, P.J.; Jackson, A.U.; Bragg-Gresham, J.L.; Vitart, V.; Marten, J.; Navarro, P.; Bellis, C.; Pasko, D.; Johansson, A.; Snitker, S.; Cheng, Y.-C.; Eriksson, J.; Lim, U.; Aadahl, M.; Adair, L.S.; Amin, N.; Balkau, B.; Auvinen, J.; Beilby, J.; Bergman, R.N.; Bergmann, S.; Bertoni, A.G.; Blangero, J.; Bonnefond, A.; Bonnycastle, L.L.; Borja, J.B.; Brage, S.; Busonero, F.; Buyske, S.; Campbell, H.; Chines, P.S.; Collins, F.S.; Corre, T.; Smith, G.D.; Delgado, G.E.; Dueker, N.; Dorr, M.; Ebeling, T.; Eiriksdottir, G.; Esko, T.; Faul, J.D.; Fu, M.; Faerch, K.; Gieger, C.; Glaser, S.; Gong, J.; Gordon-Larsen, P.; Grallert, H.; Grammer, T.B.; Grarup, N.; van Grootheest, G.; Harald, K.; Hastie, N.D.; Havulinna, A.S.; Hernandez, D.; Hindorff, L.; Hocking, L.J.; Holmens, O.L.; Holzapfel, C.; Hottenga, J.J.; Huang, J.; Huang, T.; Hui, J.; Huth, C.; Hutri-Kahonen, N.; James, A.L.; Jansson, J.-O.; Jhun, M.A.; Juonala, M.; Kinnunen, L.; Koistinen, H.A.; Kolcic, I.; Komulainen, P.; Kuusisto, J.; Kvaloy, K.; Kahonen, M.; Lakka, T.A.; Launer, L.J.; Lehne, B.; Lindgren, C.M.; Lorentzon, M.; Luben, R.; Marre, M.; Milaneschi, Y.; Monda, K.L.; Montgomery, G.W.; De Moor, M.H.M.; Mulas, A.; Muller-Nurasyid, M.; Musk, A.W.; Mannikko, R.; Mannisto, S.; Narisu, N.; Nauck, M.; Nettleton, J.A.; Nolte, I.M.; Oldehinkel, A.J.; Olden, M.; Ong, K.K.; Padmanabhan, S.; Paternoster, L.; Perez, J.; Perola, M.; Peters, A.; Peters, U.; Peyser, P.A.; Prokopenko, I.; Puolijoki, H.; Raitakari, O.T.; Rankinen, T.; Rasmussen-Torvik, L.J.; Rawal, R.; Ridker, P.M.; Rose, L.M.; Rudan, I.; Sarti, C.; Sarzynski, M.A.; Savonen, K.; Scott, W.R.; Sanna, S.; Shuldiner, A.R.; Sidney, S.; Silbernagel, G.; Smith, B.H.; Smith, J.A.; Snieder, H.; Stancakova, A.; Sternfeld, B.; Swift, A.J.; Tammelin, T.; Tan, S.-T.; Thorand, B.; Thuillier, D.; Vandenput, L.; Vestergaard, H.; van Vliet-Ostaptchouk, J.V.; Vohl, M.-C.; Volker, U.; Waeber, G.; Walker, M.; Wild, S.; Wong, A.; Wright, A.F.; Zillikens, M.C.; Zubair, N.; Haiman, C.A.; Lemarchand, L.; Gyllensten, U.; Ohlsson, C.; Hofman, A.; Rivadeneira, F.; Uitterlinden, A.G.; Perusse, L.; Wilson, J.F.; Hayward, C.; Polasek, O.; Cucca, F.; Hveem, K.; Hartman, C.A.; Tonjes, A.; Bandinelli, S.; Palmer, L.J.; Kardia, S.L.R.; Rauramaa, R.; Sorensen, T.I.A.; Tuomilehto, J.; Salomaa, V.; Penninx, B.W.J.H.; de Geus, E.J.C.; Boomsma, D.I.; Lehtimaki, T.; Mangino, M.; Laakso, M.; Bouchard, C.; Martin, N.G.; Kuh, D.; Liu, Y.; Linneberg, A.; Marz, W.; Strauch, K.; Kivimaki, M.; Harris, T.B.; Gudnason, V.; Volzke, H.; Qi, L.; Jarvelin, M.-R.; Chambers, J.C.; Kooner, J.S.; Froguel, P.; Kooperberg, C.; Vollenweider, P.; Hallmans, G.; Hansen, T.; Pedersen, O.; Metspalu, A.; Wareham, N.J.; Langenberg, C.; Weir, D.R.; Porteous, D.J.; Boerwinkle, E.; Chasman, D.I.; Abecasis, G.R.; Barroso, I.; McCarthy, M.I.; Frayling, T.M.; O'Connell, J.R.; van Duijn, C.M.; Boehnke, M.; Heid, I.M.; Mohlke, K.L.; Strachan, D.P.; Fox, C.S.; Liu, C.-T.; Hirschhorn, J.N.; Klein, R.J.; Johnson, A.D.; Borecki, I.B.; Franks, P.W.; North, K.E.; Cupples, L.A.; Loos, R.J.F.; Kilpelainen, T.O. url  doi
  Title Genome-wide physical activity interactions in adiposity – A meta-analysis of 200,452 adults Type Meta-Analysis
  Year 2017 Publication PLoS Genetics Abbreviated Journal PLoS Genet  
  Volume 13 Issue (up) 4 Pages e1006528  
  Keywords Adiposity/*genetics/physiology; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/*genetics; Body Mass Index; Epigenomics; *Exercise; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Male; Obesity/*genetics/physiopathology; Waist Circumference; Waist-Hip Ratio  
  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.  
  Address The Department of Preventive Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, United States of America  
  Corporate Author PAGE Consortium Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1553-7390 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28448500; PMCID:PMC5407576 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1909  
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