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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #348604
Research Project: Genomics, Nutrition, and Health

Location: Jean Mayer Human Nutrition Research Center On Aging

Title: Gene x dietary pattern interactions in obesity: analysis of up to 68,317 adults of European ancestry

Author
item NETTLETON, JENNIFER - UNIVERSITY OF TEXAS
item FOLLIS, JACK - UNIVERSITY OF ST. THOMAS
item NGWA, JULIUS - BOSTON UNIVERSITY
item SMITH, CAREN - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY
item SHAFQAT, AHMAD - LUND UNIVERSITY
item TANAKA, TOSHIKO - NATIONAL INSTITUTE ON AGING (NIA, NIH)
item WOJCZYNSKI, MARY - WASHINGTON UNIVERSITY
item VOORTMAN, TRUDY - ERASMUS MEDICAL CENTER
item LEMAITRE, ROZENN - UNIVERSITY OF WASHINGTON
item KRISTIANSSON, KATI - NATIONAL INSTITUTE FOR HEALTH AND WELFARE (HELSINKI)
item NUOTIO, MARJA-LIISA - NATIONAL INSTITUTE FOR HEALTH AND WELFARE (HELSINKI)
item HOUSTON, DENISE - WAKE FOREST UNIVERSITY
item PERALA, MIA-MARIA - NATIONAL INSTITUTE FOR HEALTH AND WELFARE (HELSINKI)
item QI, QIBIN - HARVARD UNIVERSITY
item SONESTEDT, EMILY - LUND UNIVERSITY
item MANICHAIKUL, ANI - UNIVERSITY OF VIRGINIA
item KANONI, STAVROULA - QUEEN MARY UNIVERSITY OF LONDON
item GANNA, ANDREA - KAROLINSKA INSTITUTE
item MIKKILA, VERA - UNIVERSITY OF HELSINKI
item NORTH, KARI - UNIVERSITY OF NORTH CAROLINA
item SISCOVICK, DAVID - NEW YORK ACADEMY OF MEDICINE
item HARALD, KENNET - NATIONAL INSTITUTE FOR HEALTH AND WELFARE (HELSINKI)
item MCKEOWN, NICOLA - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY
item JOHANSSON, INGEGERD - UNIVERSITY OF UMEA
item RISSANEN, HARRI - NATIONAL INSTITUTE FOR HEALTH AND WELFARE (HELSINKI)
item LIU, YONGMEI - WAKE FOREST UNIVERSITY
item LAHTI, JARI - UNIVERSITY OF HELSINKI
item HU, FRANK - HARVARD UNIVERSITY
item BANDINELLI, STEFANIA - AZIENDA SANITARIA DI FIRENZE
item RUKH, GULL - LUND UNIVERSITY
item RICH, STEPHEN - UNIVERSITY OF VIRGINIA
item BOOIJ, LISANNE - ERASMUS MEDICAL CENTER
item DMITRIOU, MARIA - HAROKOPIO UNIVERSITY OF ATHENS
item AX, ERIKA - UPPSALA UNIVERSITY
item RAITAKARI, OLLI - UNIVERSITY OF TURKU
item MUKAMAL, KENNETH - BETH ISRAEL DEACONESS HOSPITAL
item MANNISTO, SATU - NATIONAL INSTITUTE FOR HEALTH AND WELFARE (HELSINKI)
item HALLMANS, GORAN - UNIVERSITY OF UMEA
item JULA, ANTII - NATIONAL INSTITUTE FOR HEALTH AND WELFARE (HELSINKI)
item ERICSON, ULRIKA - LUND UNIVERSITY
item JACOBS, DAVID - UNIVERSITY OF MINNESOTA
item VAN ROOIJ, FRANK - UNIVERSITY MEDICAL CENTER - UTRECHT
item DELOUKAS, PANOS - WELLCOME TRUST SANGER INSTITUTE
item SJOGREN, PER - UPPSALA UNIVERSITY
item KAHONEN, MIKA - UNIVERSITY OF TAMPERE
item DJOUSSE, LUC - HARVARD UNIVERSITY
item PEROLA, MARKUS - UNIVERSITY OF HELSINKI
item BARROSO, INES - WELLCOME TRUST SANGER INSTITUTE
item HOFMAN, ALBERT - UNIVERSITY MEDICAL CENTER - UTRECHT
item STIRRUPS, KATHLEEN - QUEEN MARY UNIVERSITY OF LONDON
item VIIKARI, JORMA - UNIVERSITY OF TURKU
item UITTERLINDEN, ANDRE - ERASMUS MEDICAL CENTER
item KALAFATI, IOANNA - HAROKOPIO UNIVERSITY OF ATHENS
item FRANCO, OSCAR - UNIVERSITY MEDICAL CENTER UTRECHT
item MOZAFFARIAN, DARIUSH - FRIEDMAN SCHOOL AT TUFTS
item SALOMAA, VEIKKO - NATIONAL INSTITUTE FOR HEALTH AND WELFARE (HELSINKI)
item BORECKI, INGRID - WASHINGTON UNIVERSITY
item KNEKT, PAUL - NATIONAL INSTITUTES OF HEALTH (NIH)
item KRITCHEVSKY, STEPHEN - WAKE FOREST UNIVERSITY
item ERIKSSON, JOHAN - NATIONAL INSTITUTES OF HEALTH (NIH)
item DEDOUSSIS, GEORGE - HAROKOPIO UNIVERSITY OF ATHENS
item QI, LU - HARVARD UNIVERSITY
item FERRUCCI, LUIGI - NATIONAL INSTITUTE ON AGING (NIA, NIH)
item ORHO-MELANDER, MARJU - LUND UNIVERSITY
item ZILLIKENS, M CAROLA - ERASMUS MEDICAL CENTER
item INGELSSON, ERIK - UPPSALA UNIVERSITY
item LEHTIMAKI, TERHO - UNIVERSITY OF TAMPERE
item RENSTROM, FRIDA - THE ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
item CUPPLES, L ADRIENNE - BOSTON UNIVERSITY
item LOOS, RUTH - THE ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
item FRANKS, PAUL - UNIVERSITY OF UMEA

Submitted to: Human Molecular Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/17/2015
Publication Date: 5/20/2015
Citation: Nettleton, J.A., Follis, J.L., Ngwa, J.S., Smith, C.E., Shafqat, A., Tanaka, T., Wojczynski, M.K., Voortman, T., Lemaitre, R.N., Kristiansson, K., Nuotio, M., Houston, D.K., Perala, M., Qi, Q., Sonestedt, E., Manichaikul, A., Kanoni, S., Ganna, A., Mikkila, V., North, K.E., Siscovick, D.S., Harald, K., McKeown, N.M., Johansson, I., Rissanen, H., Liu, Y., Lahti, J., Hu, F., Bandinelli, S.B., Rukh, G., Rich, S., Booij, L., Dmitriou, M., Ax, E., Raitakari, O., Mukamal, K., Mannisto, S., Hallmans, G., Jula, A., Ericson, U., Jacobs, D.R., Van Rooij, F.J., Deloukas, P., Sjogren, P., Kahonen, M., Djousse, L., Perola, M., Barroso, I., Hofman, A., Stirrups, K., Viikari, J., Uitterlinden, A.G., Kalafati, I.P., Franco, O.H., Mozaffarian, D., Salomaa, V., Borecki, I.B., Knekt, P., Kritchevsky, S.B., Eriksson, J.G., Dedoussis, G.V., Qi, L., Ferrucci, L., Orho-Melander, M., Zillikens, M., Ingelsson, E., Lehtimaki, T., Renstrom, F., Cupples, L., Loos, R., Franks, P.W. 2015. Gene x dietary pattern interactions in obesity: analysis of up to 68,317 adults of European ancestry. Human Molecular Genetics. https://doi.org/10.1093/hmg/ddv186.

Interpretive Summary: Obesity results from a combination of factors that includes both genetics and diet. Many genetic factors that increase obesity risk have already been identified through investigation of variants distributed across the genome (genome-wide association studies or GWAS.) Whether or not the risk associated with established obesity risk factors can be ameliorated by a healthy diet is unknown, but this can be studied through "gene-diet interaction" analyses. Since the contribution of one genetic variant to obesity is usually very small, an approach that combines many variants into a "genetic score" can be more informative than testing a single variant. In the current study, we created a genetic score using 32 genetic variants that had already been shown to be associated with greater body weight and a second score with 14 variants shown to be associated with waist-hip ratio. We tested the relationship between a healthy diet score and both scores as well individual genetic variants in over 68,000 people from the U.S. and Europe. The healthy diet score was calculated based on intakes of whole grains, fish, fruits, vegetables, and nuts/seeds (considered healthy foods groups) and red/processed meats, sweets, sugar-sweetened beverages, and fried potatoes (considered less healthy food groups.) Findings were somewhat challenging to interpret and did not clearly show that a healthy diet can offset genetic obesity risk as defined by a genetic score. Neither did the study demonstrate that genetic risk completely out-weighed the benefits of a healthy diet. One conclusion is that, while our study was large, an even greater number of people may be needed to effectively detect genetic interactions that are based on scores. Alternatively, future studies might focus more closely on selected food groups, which might uncover relationships obscured by the application of a combined diet score. The long term objective of gene-diet interaction studies such as this one is to more effectively prevent obesity through the development of tailored dietary recommendations that are based on the genetic background of the individual.

Technical 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.