Dairy intake and body composition and cardiometabolic traits among adults: Mendelian randomization analysis of 182041 individuals from 18 studies: Mendelian randomization of dairy consumption working group

Authors: HUANG, TAO - PEKING UNIVERSITY; SUN, DIANJIANYI - TULANE UNIVERSITY; HEIANZA, YORIKO - TULANE UNIVERSITY; BERGHOLDT, HELLE - NAESTVED HOSPITAL; GAO, MENG - PEKING UNIVERSITY; FANG, ZHE - PEKING UNIVERSITY; DING, MING - HARVARD UNIVERSITY; FRAZIER-WOOD, ALEXIS - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); NORTH, KARI - UNIVERSITY OF NORTH CAROLINA; MAROULI, EIRINI - QUEEN MARY UNIVERSITY OF LONDON; GRAFF, MARIAELISA - UNIVERSITY OF NORTH CAROLINA; SMITH, CAREN - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; VARBO, ANETTE - RIGSHOSPITALET - COPENHAGEN UNIVERSITY HOSPITAL; LEMAITRE, ROZENN - UNIVERSITY OF WASHINGTON; CORELLA, DOLORES - UNIVERSITY OF VALENCIA; WANG, CAROLA - NATIONAL INSTITUTE FOR HEALTH AND WELFARE (HELSINKI); TJONNELAND, ANNE - DANISH CANCER SOCIETY RESEARCH CENTER; OVERVAD, KIM - AARHUS UNIVERSITY; SORENSEN, THORKILD - COPENHAGEN UNIVERSITY; FEITOSA, MARY - WASHINGTON UNIVERSITY; WOJCZYNSKI, MARY - WASHINGTON UNIVERSITY; KAHONEN, MIKA - UNIVERSITY OF TAMPERE; MIKKILA, VERA - NATIONAL INSTITUTE FOR HEALTH AND WELFARE (HELSINKI); BARTZ, TRACI - UNIVERSITY OF WASHINGTON; PSATY, BRUCE - KAISER PERMANENTE; SISCOVICK, DAVID - NEW YORK ACADEMY OF MEDICINE; DANNING, REBECCA - BRIGHAM & WOMEN'S HOSPITAL; DEDOUSSIS, GEORGE - HAROKOPIO UNIVERSITY OF ATHENS; PEDERSEN, OLUF - COPENHAGEN UNIVERSITY; HANSEN, TORBEN - COPENHAGEN UNIVERSITY; HAVULINNA, AKI - NATIONAL INSTITUTE FOR HEALTH AND WELFARE (HELSINKI); MANNISTO, SATU - NATIONAL INSTITUTE FOR HEALTH AND WELFARE (HELSINKI); ROTTER, JEROME - HARBOR-UCLA MEDICAL CENTER; SARES-JASKE, LAURA - NATIONAL INSTITUTE FOR HEALTH AND WELFARE (HELSINKI); ALLISON, MATTHEW - 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; RIDKER, PAUL - BRIGHAM & WOMEN'S HOSPITAL; VIIKARI, JORMA - UNIVERSITY OF TURKU; RAITAKARI, OLLI - UNIVERSITY OF TURKU; LEHTIMAKI, TERHO - FIMLAB LABORATORIES; HELMINEN, MIKA - UNIVERSITY OF TAMPERE; WANG, YUJIE - UNIVERSITY OF NORTH CAROLINA; DELOUKAS, PANAGIOTIS - QUEEN MARY UNIVERSITY OF LONDON; KNEKT, PAUL - NATIONAL INSTITUTE FOR HEALTH AND WELFARE (HELSINKI); KANERVA, NOORA - NATIONAL INSTITUTE FOR HEALTH AND WELFARE (HELSINKI); KILPELAINEN, TUOMAS - COPENHAGEN UNIVERSITY; PROVINCE, MICHAEL - WASHINGTON UNIVERSITY; MOZAFFARIAN, DARIUSH - TUFTS UNIVERSITY; CHASMAN, DANIEL - BRIGHAM & WOMEN'S HOSPITAL; NORDESTGAARD, BORGE - RIGSHOSPITALET - COPENHAGEN UNIVERSITY HOSPITAL; ELLERVIK, CHRISTINA - COPENHAGEN UNIVERSITY; QI, LU - TULANE UNIVERSITY

Submitted to: Clinical Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/25/2019
Publication Date: 5/28/2019
Citation: Huang, T., Sun, D., Heianza, Y., Bergholdt, H.K., Gao, M., Fang, Z., Ding, M., Frazier-Wood, A.C., North, K.E., Marouli, E., Graff, M., Smith, C.E., Varbo, A., Lemaitre, R.N., Corella, D., Wang, C.A., Tjonneland, A., Overvad, K., Sorensen, T.I., Feitosa, M.F., Wojczynski, M.K., Kahonen, M., Mikkila, V., Bartz, T.M., Psaty, B.M., Siscovick, D.S., Danning, R.D., Dedoussis, G., Pedersen, O., Hansen, T., Havulinna, A.S., Mannisto, S., Rotter, J.I., Sares-Jaske, L., Allison, M.A., Rich, S.S., Sorli, J.V., Coltell, O., Pennell, C.E., Eastwood, P., Ridker, P.M., Viikari, J., Raitakari, O., Lehtimaki, T., Helminen, M., Wang, Y., Deloukas, P., Knekt, P., Kanerva, N., Kilpelainen, T.O., Province, M.A., Mozaffarian, D., Chasman, D.I., Nordestgaard, B.G., Ellervik, C., Qi, L. 2019. Dairy intake and body composition and cardiometabolic traits among adults: Mendelian randomization analysis of 182041 individuals from 18 studies: Mendelian randomization of dairy consumption working group. Clinical Chemistry. 65(6):751-760. https://doi.org/10.1373/clinchem.2018.300335.
DOI: https://doi.org/10.1373/clinchem.2018.300335

Interpretive Summary: Dairy products are generally considered to be part of a healthy diet, but whether dairy foods specifically influence the risk of chronic diseases of aging continues to be debated. Previous observational studies have been limited in two ways. First, they rely on people to report their intakes, which can be imprecise, and second, most studies are unable to isolate the impact of dairy foods from the impact of other foods. To address both of these limitations, we used an objective estimate of dairy intake that was based on genetic measurement (genotype). Dairy foods are unusual, in that a single, common genetic variant determines whether or not people can digest lactose (the main sugar in milk) and consume dairy products over their lifetimes. People with the genetic variant can easily consume milk and other dairy products, while people without the variant cannot. Results from this genetically based approach showed that dairy intake contributed to one healthy outcome, but had no impact on other important biomarkers. Specifically, people who carried the lactose-digesting genetic variant also showed higher lean body mass, which protects against several age-related conditions. However, dairy intake did not affect lipids or blood measurements that reflect glucose metabolism. These results are important because they improve understanding of the benefits and risks of dairy intake, which may differ for different people.

Technical Abstract: Background: Associations between dairy intake and body composition and cardiometabolic traits have been inconsistently observed in epidemiological studies, and the causal relationship remains ill-defined. Methods: We performed Mendelian randomization analysis using an established genetic variant located upstream of the lactase gene (LCT-13910 C/T, rs4988235) associated with dairy intake as an instrumental variable (IV). The causal effects of dairy intake on body composition and cardiometabolic traits (lipids, glycemic traits, and inflammatory factors) were quantified by IV estimators among 182041 participants from 18 studies. Results: Each 1 serving/day higher dairy intake was associated with higher lean mass [beta (SE) = 0.117 kg (0.035); P = 0.001], higher hemoglobin A1c [0.009% (0.002); P < 0.001], lower LDL [-0.014 mmol/L (0.006); P = 0.013], total cholesterol (TC) [-0.012 mmol/L (0.005); P = 0.023], and non-HDL [-0.012 mmol/L (0.005); P = 0.028]. The LCT-13910 C/T CT + TT genotype was associated with 0.214 more dairy servings/day (SE = 0.047; P < 0.001), 0.284 cm higher waist circumference (SE = 0.118; P = 0.017), 0.112 kg higher lean mass (SE = 0.027; P = 3.8 x 10^-5), 0.032 mmol/L lower LDL (SE = 0.009; P = 0.001), and 0.032 mmol/L lower TC (SE = 0.010; P = 0.001). Genetically higher dairy intake was associated with increased lean mass [0.523 kg per serving/day (0.170); P = 0.002] after correction for multiple testing (0.05/18). However, we find that genetically higher dairy intake was not associated with lipids and glycemic traits. Conclusions: The present study provides evidence to support a potential causal effect of higher dairy intake on increased lean mass among adults. Our findings suggest that the observational associations of dairy intake with lipids and glycemic traits may be the result of confounding.