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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #345860
Title: Genome-wide interactions with dairy intake for body mass index in adults of European descent

Author
item SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item FOLLIS, JACK - University Of St Thomas
item DASHTI, HASSAN - Tufts University
item TANAKA, TOSHIKO - National Institutes Of Health (NIH)
item GRAFF, MARIAELISA - University Of North Carolina
item FRETTS, AMANDA - University Of Washington
item KILPELAINEN, TUOMAS - University Of Copenhagen
item WOJCZYNSKI, MARY - Washington University
item RICHARDSON, KRIS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item NALLS, MIKE - National Institute On Aging (NIA, NIH)
item SCHULZ, CHRISTINA-ALEXA - Lund University
item LIU, YONGMEI - Wake Forest University
item FRAZIER-WOOD, ALEXIS - Baylor College Of Medicine
item VAN EEKELEN, ESTHER - Leiden University
item WANG, CAROL - University Of Western Australia
item DE VRIES, PAUL - University Of Texas
item MIKKILA, VERA - University Of Turku
item ROHDE, REBECCA - University Of North Carolina
item PSATY, BRUCE - University Of Washington
item HANSEN, TORBEN - University Of Copenhagen
item FEITOSA, MARY - Washington University
item Lai, Chao Qiang
item HOUSTON, DENISE - Wake Forest University
item FERRUCCI, LUIGI - National Institute On Aging (NIA, NIH)
item ERICSON, ULRIKA - Lund University
item WANG, ZHE - Stanford University
item DE MUTSERT, RENEE - Leiden University
item ODDY, WENDY - University Of Tasmania
item DE JONGE, ESTER - Erasmus Medical Center
item SEPPALA, ILKKA - University Of Tampere Medical School
item JUSTICE, ANNE - University Of North Carolina
item LEMAITRE, ROZENN - University Of Washington
item SORENSEN, THORKILD - University Of Copenhagen
item PROVINCE, MICHAEL - Washington University
item Parnell, Laurence
item GARCIA, MELISSA - National Institute On Aging (NIA, NIH)
item BANDINELLI, STEFANIA - Azienda Sanitaria Di Firenze
item ORHO-MELANDER, MARJU - Lund University
item RICH, STEPHEN - University Of Virginia
item ROSENDAAL, FRITS - Leiden University
item PENNELL, CRAIG - University Of Western Australia
item KIEFTE-DEJONG, JESSICA - Erasmus Medical Center
item KAHONEN, MIKA - Tampere University Hospital
item YOUNG, KRISTEN - University Of North Carolina
item PEDERESEN, OLUF - University Of Copenhagen
item ASLIBEKYAN, STELLA - University Of Alabama
item ROTTER, JEROME - Harbor-Ucla Medical Center
item MOOK-KANAMORI, DENNIS - Leiden University
item ZILLIKENS, M - Erasmus Medical Center
item RAITAKARI, OLLI - University Of Turku
item NORTH, KARI - University Of North Carolina
item OVERVAD, KIM - Aarhus University
item ARNETT, DONNA - University Of Alabama
item HOFMAN, ALBERT - Erasmus Medical Center
item LEHTIMAKI, TERHO - Tampere University Hospital
item TJONNELAND, ANNE - Danish Cancer Society Research Center
item UITTERLINDEN, ANDRE - University Of Tampere Medical School
item RIVADENEIRA, FERNANDO - Erasmus Medical Center
item FRANCO, OSCAR - Erasmus Medical Center
item GERMAN, J. BRUCE - University Of California
item SISCOVICK, DAVID - New York Academy Of Medicine
item CUPPLES, L - Boston University
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Molecular Nutrition and Food Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/28/2017
Publication Date: 12/11/2017
Citation: Smith, C.E., Follis, J.L., Dashti, H., Tanaka, T., Graff, M., Fretts, A.M., Kilpelainen, T., Wojczynski, M., Richardson, K., Nalls, M., Schulz, C.N., Liu, Y., Frazier-Wood, A., Van Eekelen, E., Wang, C., De Vries, P.S., Mikkila, V., Rohde, R., Psaty, B.M., Hansen, T., Feitosa, M.F., Lai, C., Houston, D.K., Ferrucci, L., Ericson, U., Wang, Z., De Mutsert, R., Oddy, W.H., De Jonge, E.A., Seppala, I., Justice, A.E., Lemaitre, R.N., Sorensen, T.I., Province, M.A., Parnell, L.D., Garcia, M.E., Bandinelli, S., Orho-Melander, M., Rich, S.S., Rosendaal, F.R., Pennell, C.E., Kiefte-Dejong, J.C., Kahonen, M., Young, K.L., Pederesen, O., Aslibekyan, S., Rotter, J.I., Mook-Kanamori, D.O., Zillikens, M.C., Raitakari, O.T., North, K.E., Overvad, K., Arnett, D.K., Hofman, A., Lehtimaki, T., Tjonneland, A., Uitterlinden, A.G., Rivadeneira, F., Franco, O.H., German, J., Siscovick, D.S., Cupples, L.A., Ordovas, J.M. 2017. Genome-wide interactions with dairy intake for body mass index in adults of European descent. Molecular Nutrition and Food Research. https://doi.org/10.1002/mnfr.201700347.
DOI: https://doi.org/10.1002/mnfr.201700347

Interpretive Summary: Obesity is a product of genetic and dietary factors, and among the dietary factors, certain food groups have been shown to modify obesity risk. In particular, dairy products have been reported to be associated with increases, decreases or neutral effects on body weight. We hypothesized that genetic factors contribute to differences in how foods affect body mass index (BMI) in different people. To investigate this hypothesis, we examined relationships between dairy products of different forms (low fat, high fat and total) and genetic variants across the whole genome. When we combined results from analysis in 9 studies (up to 25,513 individuals of European descent, living in Europe or the US), we identified six genetic sites that affected people's BMI in the context of dairy food intake. In other words, depending on the presence or absence or these variants, BMI may be higher or lower with greater intake of dairy foods. In order to strengthen this evidence of a gene-diet interaction, we then evaluated the same six variants in a set of four new cohort studies, totaling up to 17,675 European and Australian people. Of the six genetic variants, one showed a similar interaction in the new cohorts in that the presence of the variant was associated with lower BMI in people who consumed more dairy products. These findings increase our understanding of how genetics and diet act together to promote or prevent weight gain and may eventually have implications for dietary recommendations that make use of genetic information.

Technical Abstract: Scope: Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption. Methods and results: We conducted a genome-wide interaction study to discover genetic variants that account for variation in BMI in the context of low-fat, high-fat and total dairy intake in cross-sectional analysis. Data from 9 discovery studies (up to 25,513 European descent individuals) were meta-analyzed. Twenty-six genetic variants reached the selected significance threshold (P-interaction <10^-7), and six independent variants (LINC01512-rs7751666, PALM2/AKAP2-rs914359, ACTA2-rs1388, PPP1R12A-rs7961195, LINC00333-rs9635058, AC098847.1-rs1791355) were evaluated meta-analytically for replication of interaction in up to 17,675 individuals. Variant rs9635058 (128 kb 3' of LINC00333) was replicated (P-interaction =0.004). In the discovery cohorts, rs9635058 interacted with dairy (P-interaction=7.36 x 10^-8) such that each serving of low-fat dairy was associated with 0.225 kg/m2 lower BMI per each additional copy of the effect allele (A). A second genetic variant (ACTA2-rs1388) approached interaction replication significance for low-fat dairy exposure. Conclusions: Body weight responses to dairy intake may be modified by genotype, in that greater dairy intake may protect a genetic subgroup from higher body weight.