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

Authors: HUANG, TAO - PEKING UNIVERSITY; DING, MING - HARVARD SCHOOL OF PUBLIC HEALTH; BERGHOLDT, HELLE - UNIVERSITY OF COPENHAGEN; WANG, TIANGE - TULANE UNIVERSITY; HEIANZA, YORIKO - TULANE UNIVERSITY; SUN, DIANJIANYI - TULANE UNIVERSITY; FRAZIER-WOOD, ALEXIS - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); ASILIBEKYAN, STELLA - UNIVERSITY OF ALABAMA; NORTH, KARI - UNIVERSITY OF NORTH CAROLINA; VOORTMAN, TRUDY - ERASMUS MEDICAL CENTER; GRAFF, MARIA - UNIVERSITY OF NORTH CAROLINA; SMITH, CAREN - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; LAI, CHAO - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; VARBO, ANETTE - UNIVERSITY OF COPENHAGEN; LEMAITRE, ROZENN - UNIVERSITY OF WASHINGTON; DE JONGE, M - ERASMUS MEDICAL CENTER; FUMERON, FREDERIC - CORDELIER RESEARCH CENTER; CORELLA, DOLORES - UNIVERSITY OF VALENCIA; WANG, CAROL - UNIVERSITY OF WESTERN AUSTRALIA; TJONNELAND, ANNE - DANISH CANCER SOCIETY RESEARCH CENTER; OVERAD, KIM - AARHUS UNIVERSITY; SORENSEN, THORKILD - UNIVERSITY OF COPENHAGEN; FEITOSA, MARY - WASHINGTON UNIVERSITY SCHOOL OF MEDICINE; WOJCZYNSKI, MARY - WASHINGTON UNIVERSITY SCHOOL OF MEDICINE; KAHONEN, MIKA - TAMPERE UNIVERSITY HOSPITAL; RENSTROM, FRIDA - LUND UNIVERSITY; PSATY, BRUCE - UNIVERSITY OF WASHINGTON; SISCOVICK, DAVID - NEW YORK ACADEMY OF MEDICINE; BARROSO, INES - WELLCOME TRUST SANGER INSTITUTE; JOHANSSON, INGEGERD - UNIVERSITY OF UMEA; HERNANDEZ, DENA - NATIONAL INSTITUTE ON AGING (NIA, NIH); FERUCCI, LUIGI - NATIONAL INSTITUTE ON AGING (NIA, NIH); BANDINELLI, STEFANIA - AZIENDA SANITARIA DI FIRENZE; LINNEBERG, ALLAN - RESEARCH CENTRE FOR PREVENTION AND HEALTH; ZILLIKENS, M - ERASMUS MEDICAL CENTER; SANDHOLT, CAMILLA - UNIVERSITY OF COPENHAGEN; PEDERSEN, OLUF - UNIVERSITY OF COPENHAGEN; HANSEN, TORBEN - UNIVERSITY OF COPENHAGEN; SCHULZ, CHRISTINA - LUND UNIVERSITY; SONESTEDT, EMILY - LUND UNIVERSITY; ORHO-MELANDER, MARJU - LUND UNIVERSITY; CHEN, TZU - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); ROTTER, JEROME - HARBOR-UCLA MEDICAL CENTER; ALLISON, MATHEW - UNIVERSITY OF CALIFORNIA; RICH, STEPHEN - UNIVERSITY OF VIRGINIA; SORLI, JOSE - UNIVERSITY OF VALENCIA; COLTELL, OSCAR - INSTITUTO DE SALUD CARLOS III; 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 - BRIGHAM & WOMEN'S HOSPITAL; RIDKER, PAUL - BRIGHAM & WOMEN'S HOSPITAL; VIIKARI, JORMA - UNIVERSITY OF TURKU; RAITAKARI, OLLI - UNIVERSITY OF TURKU; LEHTIMAKI, TERHO - UNIVERSITY OF TAMPERE; MIKKILA, VERA - UNIVERSITY OF TURKU; WILLETT, WALTER - HARVARD SCHOOL OF PUBLIC HEALTH; WANG, YUJIE - UNIVERSITY OF NORTH CAROLINA; TUCKER, KATHERINE - UNIVERSITY OF MASSACHUSETTS; ORDOVAS, JOSE - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; KILPELAINEN, TUOMAS - UNIVERSITY OF COPENHAGEN; PROVINCE, MICHAEL - WASHINGTON UNIVERSITY SCHOOL OF MEDICINE; FRANKS, PAUL - HARVARD SCHOOL OF PUBLIC HEALTH; ARNETT, DONNA - UNIVERSITY OF KENTUCKY; 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; MOZAFFARIAN, DARIUSH - TUFTS UNIVERSITY; HU, FRANK - HARVARD SCHOOL OF PUBLIC HEALTH; CHASMAN, DANIEL - BRIGHAM & WOMEN'S HOSPITAL; NORDESTGAARD, BORGE - UNIVERSITY OF COPENHAGEN; ELLERVIK, CHRISTINA - UNIVERSITY OF COPENHAGEN; 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.