Genome-wide analysis of BMI in adolescents and young adults reveals additional insight into the effects of genetic loci over the life course
Year: 2013
Type: review
Abstract: Genetic loci for body mass index (BMI) in adolescence and young adulthood, a period of high risk for weight gain, are understudied, yet may yield important insight into the etiology of obesity and early intervention. To identify novel genetic loci and examine the influence of known loci on BMI during this critical time period in late adolescence and early adulthood, we performed a two-stage meta-analysis using 14 genome-wide association studies in populations of European ancestry with data on BMI between ages 16 and 25 in up to 29 880 individuals. We identified seven independent loci (P < 5.0 × 10⁻⁸) near FTO (P = 3.72 × 10⁻²³), TMEM18 (P = 3.24 × 10⁻¹⁷), MC4R (P = 4.41 × 10⁻¹⁷), TNNI3K (P = 4.32 × 10⁻¹¹), SEC16B (P = 6.24 × 10⁻⁹), GNPDA2 (P = 1.11 × 10⁻⁸) and POMC (P = 4.94 × 10⁻⁸) as well as a potential secondary signal at the POMC locus (rs2118404, P = 2.4 × 10⁻⁵ after conditioning on the established single-nucleotide polymorphism at this locus) in adolescents and young adults. To evaluate the impact of the established genetic loci on BMI at these young ages, we examined differences between the effect sizes of 32 published BMI loci in European adult populations (aged 18-90) and those observed in our adolescent and young adult meta-analysis. Four loci (near PRKD1, TNNI3K, SEC16B and CADM2) had larger effects and one locus (near SH2B1) had a smaller effect on BMI during adolescence and young adulthood compared with older adults (P < 0.05). These results suggest that genetic loci for BMI can vary in their effects across the life course, underlying the importance of evaluating BMI at different ages.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/ddt205
Authors: Mariaelisa Graff, Julius S. Ngwa, Tsegaselassie Workalemahu, Georg Homuth, Sabine Schipf, Alexander Teumer, Henry Völzke, Henri Wallaschofski, Goncalo R. Abecasis, Lakatta Edward, Cucca Francesco, Serena Sanna, Paul Scheet, David Schlessinger, Carlo Sidore, Xiangjun Xiao, Zhaoming Wang, Stephen J. Chanock, Kevin B. Jacobs, Richard B. Hayes, Frank Hu, Rob M. Van Dam, Richard J. Crout, Mary L. Marazita, John R Shaffer, Larry D. Atwood, Caroline S. Fox, Nancy L. Heard-Costa, Charles White, Audrey C. Choh, Stefan A. Czerwinski, Ellen W. Demerath, Thomas D. Dyer, Bradford Towne, Najaf Amin, Ben A. Oostra, Cornelia M. Van Duijn, M. Carola Zillikens, Tõnu Esko, Mari Nelis, Tit Nikopensius, Andres Metspalu, David P. Strachan, Keri Monda, Lu Qi, Kari E. North, L. Adrienne Cupples, Penny Gordon-Larsen, Sonja I. Berndt
Institutions: University of North Carolina at Chapel Hill, Boston University, Harvard University, Universität Greifswald, Universitätsmedizin Greifswald, University of Michigan, National Institute on Aging, Institute of Genetic and Biomedical Research, National Research Council, National Institutes of Health, Division of Cancer Epidemiology and Genetics, Science Applications International Corporation (United States), NYU Langone Health, New York University, Brigham and Women's Hospital, National University of Singapore, West Virginia University, University of Pittsburgh, Framingham Heart Study, Wright State University, University of Minnesota, Texas Biomedical Research Institute, Centre for Medical Systems Biology, Erasmus MC, Estonian Biocentre, University of Tartu, University of Geneva, St George's, University of London, Amgen (United States)
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funders: Juvenile Diabetes Research Foundation International, American Heart Association, School of Medicine, Boston University, Johns Hopkins University, University of Pittsburgh, West Virginia University, Wellcome Trust, European Commission, Bundesministerium für Bildung und Forschung, Tartu Ülikool, Hersenstichting, Centre for Medical Systems Biology, Universität Greifswald, Ministry of Cultural Affairs, National Institutes of Health, U.S. Public Health Service, Medical Research Council, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Child Health and Human Development, National Institute of Dental and Craniofacial Research, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Division of Cancer Epidemiology and Genetics, National Cancer Institute
Awards: G1083489883, G1137313802, G118440752, Nutrition Sciences and Health, Carolina Population Center, G1293366060, G136105103, Obesity Genes, Energy Regulation in Response to Weight-Loss Diets, G1449130676, G1466586219, G1518085888, G1543486331, G1663676665, G1664136512, G1689944598, G1789099407, G1861783600, G1975277730, FIELD CENTER FOR CCSP, G2064885621, Genetic Markers of CHD in Type 2 Diabetes, G2098337849, G2146332128, G215333750, CCSP FIELD CENTER, G2178492673, Verbundprojekt: Spitzenforschung und Innovation in den Neuen Ländern - GANI_MED - Greifswald Approach to Individualized Medicine, Institute for Clinical and Translational Research (UL1), G250621538, G25881238, G2824707892, G2918387404, G3042145041, G3153491656, G3205625555, G3227761751, G3349769430, G3436481580, G3588481721, Exome Variants Underlying Weight Gain from Adolescence to Adulthood, G36937976, Boston Nutrition Obesity Research Center, G3721894273, GWA for Gene-Environment Interaction Effects Influencing CHD, G3868930229, Dental Caries: Whole Genome Association and Gene x Environment Studies, Genetic Regulation of Adiposity and Associated CVD Risks, G395403786, COMMUNITY AND COHORT SURVEILLANCE PROGRAM, G4140938724, G4145745212, Adiposity, Disease Risk Factors, and Lifetime Health, G4174427447, G4178577773, G4383452904, Factors Contributing to Oral Health Disparities in Appalachia, Genome Wide Association Coordinating Center, G4671189754, Anwendung von DNA-Array-Technologien in Molekularer Medizin und Mikrobiologie, G4805355505, G4824283243, G4932516547, Verbesserung der Leistungsfähigkeit der klinischen Forschung besonders in den Schwerpunkten Community Medicine und Molekulare Medizin, Phase II, FIELD CENTER, G5233356934, G528395701, CCSP - FIELD CENTER AND ULTRASOUND READING CENTER, G5369020747, Genome-Wide Association for Loci Influencing CHD and Other Heart, Lung and Blood, G5502349062, G5522185877, Epidemiology of Venous Thrombosis and Pulmonary Embolism, G5568298347, G5622977475, A national DNA control series for genetic case-control studies based on the British 1958 birth cohort, COMMUNITY AND COHORT SURVEILLANCE PROGRAMS, CHARGE consortium: omics discovery for CVD and aging phenotypes, G6029994567, G6196377753, G6204895930, G6255202575, G632409923, Type 1 Diabetes Genetics Consortium, G6413504379, G6576172577, G6661414329, G67356480, G6832097205, G6860406196, THE FRAMINGHAM HEART STUDY-N01HC25195-268025195-268025195, G6902273418, G7028328829, G7093047072, G7364523043, G7453583093, G7627314639, G7693351332, G77250574, G786153652, G793702358, CENTRAL HEMOSTATIS LABORATORY FOR CCSP, G80149192, Genetic Analysis of Osteoporosis Risk Factors, G8123125509, G8161118679, G8267674335, G8276458029, The Genetics of Infant Growth and Later Obesity, Verbesserung der Struktur- und Leistungsfähigkeit der klinischen Forschung besonders in den Schwerpunkten Community Medicine und Molekulare Medizin, G88852782, The genetics of weight, BMI, adiposity and obesity, G9000015747, G9000028264, G9000029955, G9000080822, G9000108254, G9000124674, G9000126117, G9000152345, G9000294209, From GWAS loci to blood pressure genes, variants & mechanisms - Renewal, G915808470, G947029668, G985071772
OpenAlex ID: W2119459661