Dataset Information

Gene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry.

ABSTRACT: Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjusted WHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjusted WHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.

SUBMITTER: Nettleton JA

PROVIDER: S-EPMC4512626 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Gene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry.

Nettleton Jennifer A JA Follis Jack L JL Ngwa Julius S JS Smith Caren E CE Ahmad Shafqat S Tanaka Toshiko T Wojczynski Mary K MK Voortman Trudy T Lemaitre Rozenn N RN Kristiansson Kati K Nuotio Marja-Liisa ML Houston Denise K DK Perälä Mia-Maria MM Qi Qibin Q Sonestedt Emily E Manichaikul Ani A Kanoni Stavroula S Ganna Andrea A Mikkilä Vera V North Kari E KE Siscovick David S DS Harald Kennet K Mckeown Nicola M NM Johansson Ingegerd I Rissanen Harri H Liu Yongmei Y Lahti Jari J Hu Frank B FB Bandinelli Stefania S Rukh Gull G Rich Stephen S Booij Lisanne L Dmitriou Maria M Ax Erika E Raitakari Olli O Mukamal Kenneth K Männistö Satu S Hallmans Göran G Jula Antti A Ericson Ulrika U Jacobs David R DR Van Rooij Frank J A FJ Deloukas Panos P Sjögren Per P Kähönen Mika M Djousse Luc L Perola Markus M Barroso Inês I Hofman Albert A Stirrups Kathleen K Viikari Jorma J Uitterlinden André G AG Kalafati Ioanna P IP Franco Oscar H OH Mozaffarian Dariush D Salomaa Veikko V Borecki Ingrid B IB Knekt Paul P Kritchevsky Stephen B SB Eriksson Johan G JG Dedoussis George V GV Qi Lu L Ferrucci Luigi L Orho-Melander Marju M Zillikens M Carola MC Ingelsson Erik E Lehtimäki Terho T Renström Frida F Cupples L Adrienne LA Loos Ruth J F RJ Franks Paul W PW

Human molecular genetics 20150520 16

Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317 ...[more]

PMID: 25994509

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Project description:Obesity is a chronic metabolic disease characterised by an increase of body fat stores. It is a gateway to ill health, and it has become one of the leading causes of disability and death, affecting not only adults but also children and adolescents worldwide. In clinical practice, the body fatness is estimated by BMI, and the accumulation of intra-abdominal fat (marker for higher metabolic and cardiovascular disease risk) can be assessed by waist circumference. Complex interactions between biological, behavioural, social and environmental factors are involved in regulation of energy balance and fat stores. A comprehensive history, physical examination and laboratory assessment relevant to the patient's obesity should be obtained. Appropriate goals of weight management emphasise realistic weight loss to achieve a reduction in health risks and should include promotion of weight loss, maintenance and prevention of weight regain. Management of co-morbidities and improving quality of life of obese patients are also included in treatment aims. Balanced hypocaloric diets result in clinically meaningful weight loss regardless of which macronutrients they emphasise. Aerobic training is the optimal mode of exercise for reducing fat mass while a programme including resistance training is needed for increasing lean mass in middle-aged and overweight/obese individuals. Cognitive behavioural therapy directly addresses behaviours that require change for successful weight loss and weight loss maintenance. Pharmacotherapy can help patients to maintain compliance and ameliorate obesity-related health risks. Surgery is the most effective treatment for morbid obesity in terms of long-term weight loss. A comprehensive obesity management can only be accomplished by a multidisciplinary obesity management team. We conclude that physicians have a responsibility to recognise obesity as a disease and help obese patients with appropriate prevention and treatment. Treatment should be based on good clinical care, and evidence-based interventions; should focus on realistic goals and lifelong multidisciplinary management.

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Dataset Information

Gene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry.

Publications

Gene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry.

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