Dairy consumption and body mass index among adults: Mendelian randomization analysis of 184802 individuals from 25 studies

Authors: HUANG, TAO - Harvard University; DING, MING - Harvard University; BERGHOLDT, HELLE - University Of Copenhagen; WANG, TIANGE - Tulane University; HEIANZA, YORIKO - Tulane University; SUN, DIANJIANYL - Tulane University; FRAZIER-WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); ASLIBEKYAN, STELLA - University Of Alabama; NORTH, KARI - University Of North Carolina; VOORTMAN, TRUDY - Erasmus Medical Center; GRAFF, MARIAELISA - University Of North Carolina; SMITH, CAREN E - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; Lai, Chao Qiang; VARBO, ANETTE - University Of Copenhagen; LEMAITRE, ROZENN - University Of Washington; DE JONGE, M. ESTER - Erasmus Medical Center; FUMERON, FRÉDÉRIC - Cordelier Research Center; CORELLA, DOLORES - University Of Valencia; WANG, CAROL - University Of Western Australia; TJØNNELAND, ANNE - Danish Cancer Society Research Center; OVERVAD, KIM - Aarhus University; SØRENSEN, THORKILD - University Of Copenhagen; FEITOSA, MARY - Washington University; WOJCZYNSKI, MARY - Washington University; KÄHÖNEN, MIKA - Tampere University Hospital; RENSTRÖM, FRIDA - Lund University; PSATY, BRUCE - University Of Washington; SISCOVICK, DAVID - New York Academy Of Medicine; BARROSO, INÊS - Wellcome Trust Sanger Institute; JOHANSSON, INGEGERD - University Of Umea; HERNANDEZ, DENA - National Institute On Aging (NIA, NIH); FERRUCCI, LUIGI - National Institute On Aging (NIA, NIH); BANDINELLI, STEFANIA - Azienda Sanitaria Di Firenze; LINNEBERG, ALLAN - Research Centre For Prevention And Health; ZILLIKENS, M. CAROLA - Erasmus Medical Center; SANDHOLT, CAMILLA HELENE - University Of Copenhagen; PEDERSON, OLUF - University Of Copenhagen; HANSEN, TORBEN - University Of Copenhagen; SCHULZ, CHRISTINA- - Lund University; SONESTEDT, EMILY - Lund University; ORHO-MELANDER, MARJU - Lund University; CHEN, TZU-AN - Children'S Nutrition Research Center (CNRC); ROTTER, JEROME - Los Angeles Biomedical Research Institute; ALLISON, MATTHEW - University Of California; RICH, STEPHEN - University Of Virginia; SORLI, JOSE - University Of Valencia; COLTELL, OSCAR - University Jaume I Of Castellon; PENNELL, CRAIG - University Of Western Australia; EASTWOOD, PETER - University Of Western Australia; HOFMAN, ALBERT - Erasmus Medical Center; UITTERLINDEN, ANDRE - Erasmus Medical Center; VAN ROOIJ, FRANK - Erasmus Medical Center; CHU, AUDREY - Brigham & Women'S Hospital; ROSE, LYNDA - Harvard University; RIDKER, PAUL - Brigham & Women'S Hospital; VIIKARI, JORMA - University Of Turku; RAITAKARI, OLLI - University Of Turku; LEHTIMÄKI, TERHO - University Of Tampere Medical School; MIKKILÄ, VERA - University Of Helsinki; WILLET, WALTER - Harvard University; WANG, YUJIE - University Of North Carolina; TUCKER, KATHERINE - University Of Massachusetts; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; KILPELÄINEN, TUOMAS - University Of Copenhagen; PROVINCE, MICHAEL - Washington University; FRANKS, PAUL - Lund University; ARNETT, DONNA - University Of Alabama; TANAKA, TOSHIKO - National Institute On Aging (NIA, NIH); TOFT, ULLA - Research Centre For Prevention And Health; ERICSON, ULRIKA - Lund University; FRANCO, OSCAR - Erasmus Medical Center; MAZAFFARIAN, DARIUSH - Tufts University; HU, FRANK - Harvard University; CHASMAN, DANIEL - Harvard University; NORDESTGAARD, BØRGE - University Of Copenhagen; ELLERVIK, CHRISTINA - Boston Children'S Hospital; QI, LU - Tulane University

Submitted to: Clinical Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/31/2017
Publication Date: 1/1/2018
Citation: Huang, T., Ding, M., Bergholdt, H.K., Wang, T., Heianza, Y., Sun, D., Frazier-Wood, A.C., Aslibekyan, S., North, K.E., Voortman, T., Graff, M., Smith, C., Lai, C., Varbo, A., Lemaitre, R.N., De Jonge, M.A., Fumeron, F., Corella, D., Wang, C.A., Tjønneland, A., Overvad, K., Sørensen, T.I., Feitosa, M.F., Wojczynski, M.K., Kähönen, M., Renström, F., Psaty, B.M., Siscovick, D.S., Barroso, I., Johansson, I., Hernandez, D., Ferrucci, L., Bandinelli, S., Linneberg, A., Zillikens, M., Sandholt, C., Pederson, O., Hansen, T., Schulz, C.A., Sonestedt, E., Orho-Melander, M., Chen, T., Rotter, J.I., Allison, M.A., Rich, S.S., Sorli, J.V., Coltell, O., Pennell, C.E., Eastwood, P., Hofman, A., Uitterlinden, A.G., Van Rooij, F.J., Chu, A.Y., Rose, L.M., Ridker, P.M., Viikari, J., Raitakari, O., Lehtimäki, T., Mikkilä, V., Willet, W.C., Wang, Y., Tucker, K.L., Ordovas, J.M., Kilpeläinen, T.O., Province, M.A., Franks, P.W., Arnett, D.K., Tanaka, T., Toft, U., Ericson, U., Franco, O.H., Mazaffarian, D., Hu, F.B., Chasman, D.I., Nordestgaard, B.G., Ellervik, C., Qi, L. 2018. Dairy consumption and body mass index among adults: Mendelian randomization analysis of 184802 individuals from 25 studies. Clinical Chemistry. 64(1):183-191. https://doi.org/10.1373/clinchem.2017.280701.
DOI: https://doi.org/10.1373/clinchem.2017.280701

Interpretive Summary: Obesity is the result of complex interactions between genetic and environmental factors with dietary intake playing a most important role. In particular dairy products have been a nutritional staple that in recent years has been under debate for their potential association with obesity. However, the current evidence in this regard is highly controversial. Therefore, new approaches are needed to definitively put to rest this debate. Our study used a genetic-based statistical approach to examine the relation between dairy products and obesity. For this purpose, we used data from 184,802 participants in 25 epidemiological studies around the world. Specifically, we determined the presence or absence of a particular genetic variant that confers lactose tolerance and allows adults to drink milk. We then examined the relationship between this variant, dairy intake and body mass index (BMI). Our analysis reveals that carriers of the genetic variant consume more dairy products than non-carriers and have a higher BMI. Therefore, the results of this extensive and innovative study suggests that consumption of dairy products may contribute to an increase in obesity risk.

Technical Abstract: Background: Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies; and the causal relationship remains ill defined. Using the Mendelian randomization (MR) approach and meta-analysis of selected randomized controlled trials (RCTs), we aimed to assess whether dairy intake was causally related to BMI. Methods: We used a genetic polymorphism in MCM6 (LCT -13910 C/T, rs4988235), located upstream of the lactase gene (LCT) as an instrumental variable (IV) for dairy intake in a MR design. Linear regression models were fitted to analyze associations between 1) dairy intake and BMI, 2) rs4988235 and dairy intake, and 3) rs4988235 and BMI in each study. The causal effect of dairy intake on BMI was quantified by IV estimators among 184,802 participants from 25 studies. We further conducted a comprehensive meta-analysis of RCTs on the effect of dairy consumption on changes in body weight among 3,007 participants in 37 RCTs. Findings: Higher dairy intake was significantly associated with higher BMI (beta = 0.03 kg/m2 per serving/day; 95% CI, 0.00-0.06; p=0.04), while the LCT -13910 C/T CT+TT genotype was significantly associated with higher dairy intake (beta = 0.20 serving/day; 95% CI, 0.14-0.25; p=3.15x10-12) and higher BMI (beta = 0.12 kg/m2; 95% CI, 0.06-0.17; p=2.11x10-5). The IV analysis showed that genetically higher dairy intake was significantly associated with higher BMI (beta = 0.60 kg/m2 per serving/day; 95% CI, 0.27-0.92; p=3.0x10-4). In addition, our systematic review of 37 RCTs indicated that higher dairy intervention significantly increased body weight in trials without energy restriction (0.36 kg, 95% CI: 0.01, 0.70), whereas significantly decreased body weight in trials with energy restriction. Interpretation: The present study provides robust evidence to support a causal effect of higher dairy intake in the absence of caloric restriction on increased BMI.