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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #347086
Title: Genome-wide interactions with dairy intake for body mass index in adults of European descent

Author
item SMITH, CAREN - TUFTS UNIVERSITY
item FOLLIS, JACK - UNIVERSITY OF ST. THOMAS
item DASHTI, HASSAN - BRIGHAM & WOMEN'S HOSPITAL
item TANAKA, TOSHIKO - NATIONAL INSTITUTE ON AGING (NIA, 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 - TUFTS UNIVERSITY
item NALLS, MIKE - NATIONAL INSTITUTE ON AGING (NIA, NIH)
item SCHULZ, CHRISTINA - SKANE UNIVERSITY HOSPITAL
item LIU, YONGMEI - WAKE FOREST UNIVERSITY
item FRAZIER-WOOD, ALEXIS - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC)

Submitted to: Molecular Nutrition and Food Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/21/2017
Publication Date: 9/21/2017
Citation: Smith, C.E., Follis, J.L., Dashti, H.S., Tanaka, T., Graff, M., Fretts, A.M., Kilpelainen, T.O., Wojczynski, M.K., Richardson, K., Nalls, M.A., Schulz, C.A., Liu, Y., Frazier-Wood, A.C., van Eekelen, E., Wang, C., de Vries, P.S., Mikkilä, V., Rohde, R., Psaty, B.M., Hansen, T., Feitosa, M.F., Lai, C.Q., Houston, D.K., Ferruci, L., Ericson, U., Wang, Z., de Mutsert, R., Oddy, W.H., de Jonge, E.A.L., Seppälä, I., Justice, A.E., Lemaitre, R.N., Sørensen, T.I.A., Province, M.A., Parnell, L.D., Garcia, M.E., Bandinelli, S., Orho-Melander, M., Rich, S.S., Rosendaal, F.R., Pennell, C.E., Kiefte-de Jong, J.C., Kähönen, M., Young, K.L., Pedersen, 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., Lehtimäki, T., Tjønneland, A., Uitterlinden, A.G., Rivadeneira, F., Franco, O.H., German, J.B., Siscovick, D.S., Cupples, L.A., Ordovás, 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.

Interpretive Summary: A moderate consumption of low-fat dairy is recommended to help adults maintain a healthy body weight, however we know that individuals' body weight respond differently to different foods – including dairy. Some people can eat certain foods and not increase their risk of weight gain, while others cannot. It is suspected that genetic variation may contribute to the effect of dairy on body weight, but the problem is that we do not know where in the genome the genes are which influence the association between dairy and body weight status. Without this information we cannot tailor advice on dairy consumption and identify those for whom it may be beneficial, and those for whom it may not. To help answer this, We analyzed genetic variation across the whole genome in 25,513 European and American individuals, who also reported their dietary intake and weight. We identified one locus where genetic variation altered the association between low-fat dairy and body weight, which was very near a gene called LINC00333. This study provides evidence that body weight changes in response to dairy intake may be modified by genotype. Hopefully, this information will help clinicians and dieticians tailor dietary advice to prevent obesity to an individual's genetic code in the future, and so make dietary advice to the fight against obesity more effective.

Technical Abstract: 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. 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. Therefore, 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.