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

Author
item HUANG, TAO - Peking University
item DING, MING - Harvard School Of Public Health
item BERGHOLDT, HELLE - University Of Copenhagen
item WANG, TIANGE - Tulane University
item HEIANZA, YORIKO - Tulane University
item SUN, DIANJIANYI - Tulane University
item FRAZIER-WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC)
item ASILIBEKYAN, STELLA - University Of Alabama
item NORTH, KARI - University Of North Carolina
item VOORTMAN, TRUDY - Erasmus Medical Center
item GRAFF, MARIA - University Of North Carolina
item SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item LAI, CHAO - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item VARBO, ANETTE - University Of Copenhagen
item LEMAITRE, ROZENN - University Of Washington
item DE JONGE, M - Erasmus Medical Center
item FUMERON, FREDERIC - Cordelier Research Center
item CORELLA, DOLORES - University Of Valencia
item WANG, CAROL - University Of Western Australia
item TJONNELAND, ANNE - Danish Cancer Society Research Center
item OVERAD, KIM - Aarhus University
item SORENSEN, THORKILD - University Of Copenhagen
item FEITOSA, MARY - Washington University School Of Medicine
item WOJCZYNSKI, MARY - Washington University School Of Medicine
item KAHONEN, MIKA - Tampere University Hospital
item RENSTROM, FRIDA - Lund University
item PSATY, BRUCE - University Of Washington
item SISCOVICK, DAVID - New York Academy Of Medicine
item BARROSO, INES - Wellcome Trust Sanger Institute
item JOHANSSON, INGEGERD - University Of Umea
item HERNANDEZ, DENA - National Institute On Aging (NIA, NIH)
item FERUCCI, LUIGI - National Institute On Aging (NIA, NIH)
item BANDINELLI, STEFANIA - Azienda Sanitaria Di Firenze
item LINNEBERG, ALLAN - Research Centre For Prevention And Health
item ZILLIKENS, M - Erasmus Medical Center
item SANDHOLT, CAMILLA - University Of Copenhagen
item PEDERSEN, OLUF - University Of Copenhagen
item HANSEN, TORBEN - University Of Copenhagen
item SCHULZ, CHRISTINA - Lund University
item SONESTEDT, EMILY - Lund University
item ORHO-MELANDER, MARJU - Lund University
item CHEN, TZU - Children'S Nutrition Research Center (CNRC)
item ROTTER, JEROME - Harbor-Ucla Medical Center
item ALLISON, MATHEW - University Of California
item RICH, STEPHEN - University Of Virginia
item SORLI, JOSE - University Of Valencia
item COLTELL, OSCAR - Instituto De Salud Carlos Iii
item PENNELL, CRAIG - University Of Western Australia
item EASTWOOD, PETER - University Of Western Australia
item HOFMAN, ALBERT - Erasmus Medical Center
item UITTERLINDEN, ANDRE - Erasmus Medical Center
item VAN ROOIJ, FRANK - Erasmus Medical Center
item CHU, AUDREY - Brigham & Women'S Hospital
item ROSE, LYNDA - Brigham & Women'S Hospital
item RIDKER, PAUL - Brigham & Women'S Hospital
item VIIKARI, JORMA - University Of Turku
item RAITAKARI, OLLI - University Of Turku
item LEHTIMAKI, TERHO - University Of Tampere
item MIKKILA, VERA - University Of Turku
item WILLETT, WALTER - Harvard School Of Public Health
item WANG, YUJIE - University Of North Carolina
item TUCKER, KATHERINE - University Of Massachusetts
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item KILPELAINEN, TUOMAS - University Of Copenhagen
item PROVINCE, MICHAEL - Washington University School Of Medicine
item FRANKS, PAUL - Harvard School Of Public Health
item ARNETT, DONNA - University Of Kentucky
item TANAKA, TOSHIKO - National Institute On Aging (NIA, NIH)
item TOFT, ULLA - Research Centre For Prevention And Health
item ERICSON, ULRIKA - Lund University
item FRANCO, OSCAR - Erasmus Medical Center
item MOZAFFARIAN, DARIUSH - Tufts University
item HU, FRANK - Harvard School Of Public Health
item CHASMAN, DANIEL - Brigham & Women'S Hospital
item NORDESTGAARD, BORGE - University Of Copenhagen
item ELLERVIK, CHRISTINA - University Of Copenhagen
item QI, LU - Tulane University

Submitted to: Clinical Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/10/2017
Publication Date: 11/29/2017
Citation: Huang, T., Ding, M., Bergholdt, H.K., Wang, T., Heianza, Y., Sun, D., Frazier-Wood, A.C., Asilibekyan, S., North, K.E., Voortman, T., Graff, M., Smith, C.E., Lai, C.Q., Varbo, A., Lemaitre, R.N., De Jonge, M.W., Fumeron, F., Corella, D., Wang, C.A., Tjonneland, A., Overad, K., Sorensen, T.I., Feitosa, M.F., Wojczynski, M.K., Kahonen, M., Renstrom, F., Psaty, B.M., Siscovick, D.S., Barroso, I., Johansson, I., Hernandez, D., Ferucci, L., Bandinelli, S., Linneberg, A., Zillikens, M.C., Sandholt, C.H., Pedersen, O., Hansen, T., Schulz, C.A., Sonestedt, E., Orho-Melander, M., Chen, T.A., 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., Lehtimaki, T., Mikkila, V., Willett, W.C., Wang, Y., Tucker, K.L., Ordovas, J.M., Kilpelainen, T.O., Province, M.A., Franks, P.W., Arnett, D.K., Tanaka, T., Toft, U., Ericson, U., Franco, O.H., Mozaffarian, D., Hu, F.B., Chasman, D.I., Nordestgaard, B.G., Ellervik, C., Qi, L. 2017. Dairy consumption and body mass index among adults: Mendelian randomization analysis of 184802 individuals from 25 studies. Clinical Chemistry. https://doi.org/10.1373/clinchem.2017.280701.

Interpretive Summary: Intake of dairy foods has been associated with body mass index (BMI) but observational studies showing this link are inconsistent: some studies report that dairy is associated with higher BMI, some studies report that dairy is associated with a lower BMI, and yet other studies report no association at all. Even when we do see, or suspect, an association the problem is that it is not clear whether the dairy itself causes a change in BMI, or whether people who eat a lot of dairy also tend to have other lifestyle behaviors and it is these behaviors which cause the association to be seen between diary and BMI. This makes is hard to know whether individuals seeking to reduce or maintain a heathy BMI, or who are at a high risk of obesity, should make efforts to consume dairy or not. To try to address this we analyzed data from over 180,000 adults across 25 studies, and looked whether dairy intake predicted BMI over time. We also performed a new type of analyses which incorporates genetic information and helps better understand whether an environmental variable (such as dairy intake) is causally associated with a health outcome (such as BMI). Our analyses confirmed that higher dairy intake was associated with higher BMI and further, our genetic analyses suggested that this association was causal. This information suggests that it will be helpful to incorporate a reduction in dairy intake in dietary guidelines for the prevention and treatment of obesity, and may be useful for healthcare practitioners who need to give guidelines on how to maintain a healthy BMI to their patients.

Technical Abstract: Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined. We performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upstream of the lactase gene (LCT-13910 C/T, rs4988235) as an instrumental variable (IV). Linear regression models were fitted to analyze associations between (a) dairy intake and BMI, (b) rs4988235 and dairy intake, and (c) rs4988235 and BMI in each study. The causal effect of dairy intake on BMI was quantified by IV estimators among 184802 participants from 25 studies. Higher dairy intake was associated with higher BMI (B=0.03 kg/m2 per serving/day; 95% CI, 0.00–0.06; P=0.04), whereas the LCT genotype with 1 or 2 T allele was significantly associated with 0.20 (95% CI, 0.14–0.25) serving/day higher dairy intake (P=3.15 x 10-12) and 0.12 (95% CI, 0.06–0.17) kg/m2 higher BMI (P=2.11 x 10-5). MR analysis showed that the genetically determined higher dairy intake was significantly associated with higher BMI (B=0.60 kg/m2 per serving/day; 95% CI, 0.27– 0.92; P=3.0 x 10-4). The present study provides strong evidence to support a causal effect of higher dairy intake on increased BMI among adults.