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Repisalud author Smith, Caren E. author Coltell, Oscar author Sorli, Jose V. author Estruch, Ramon author Angel Martinez-Gonzalez, Miguel author Salas-Salvado, Jordi author Fito, Montserrat author Aros, Fernando author Dashti, Hassan S. author Lai, Chao Q. author Miro, Leticia author Serra-Majem, Lluis author Gomez-Gracia, Enrique author Fiol, Miquel author Ros, Emilio author Aslibekyan, Stella author Hidalgo, Bertha author Neuhouser, Marian L. author Di, Chongzhi author Tucker, Katherine L. author Arnett, Donna K author Ordovas, Jose M author Corella, Dolores funder National Institutes of Health (Estados Unidos) funder NIH - National Heart, Lung, and Blood Institute (NHLBI) (Estados Unidos) funder United States Department of Agriculture. Agricultural Research Service funder Instituto de Salud Carlos III funder Ministerio de Economía y Competitividad (España) funder Jaume I University (España) funder Generalitat Valenciana (España) funder Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 2017-10-20T10:33:52Z 2017-10-20T10:33:52Z 2016 Sci Rep. 2016; 6:33188 10.1038/srep33188 2045-2322 Scientific Reports http://hdl.handle.net/20.500.13003/10195 27624874 L622407296 2-s2.0-84987723109 http://hdl.handle.net/20.500.12105/5182 383196900001 Controversy persists on the association between dairy products, especially milk, and cardiovascular diseases (CVD). Genetic proxies may improve dairy intake estimations, and clarify diet-disease relationships through Mendelian randomization. We meta-analytically (n <= 20,089) evaluated associations between a lactase persistence (LP) SNP, the minichromosome maintenance complex component 6 (MCM6)-rs3754686C>T (nonpersistence>persistence), dairy intake, and CVD biomarkers in American (Hispanics, African-American and Whites) and Mediterranean populations. Moreover, we analyzed longitudinal associations with milk, CVD and mortality in PREDIMED), a randomized Mediterranean diet (MedDiet) intervention trial (n = 7185). The MCM6-rs3754686/MCM6-rs309180 (as proxy), LP-allele (T) was strongly associated with higher milk intake, but inconsistently associated with glucose and lipids, and not associated with CVD or total mortality in the whole population. Heterogeneity analyses suggested some sex-specific associations. The T-allele was associated with higher CVD and mortality risk in women but not in men (P-sex interaction: 0.005 and 0.032, respectively), mainly in the MedDiet group. However, milk intake was not associated with CVD biomarkers, CVD or mortality either generally or in sub-groups. Although MCM6-rs3754686 is a good milk intake proxy in these populations, attributing its associations with CVD and mortality in Mediterranean women to milk is unwarranted, as other factors limiting the assumption of causality in Mendelian randomization may exist. eng FOOD-FREQUENCY QUESTIONNAIRE SINGLE-NUCLEOTIDE POLYMORPHISM LACTASE-PERSISTENCE PHENOTYPE DOSE-RESPONSE METAANALYSIS METABOLIC RISK-FACTORS DAIRY CONSUMPTION UNITED-STATES PUERTO-RICAN BODY-WEIGHT DIET Associations of the MCM6-rs3754686 proxy for milk intake in Mediterranean and American populations with cardiovascular biomarkers, disease and mortality: Mendelian randomization research article URL https://repisalud.isciii.es/bitstreams/adfe3894-8358-46db-9e0f-11b0dc5ec361/download File MD5 f13f8d9bb0e0b0f666477f2ab0513cc3 1234728 application/pdf AssociationsOfTheMCM6-rs3754686_2016 URL https://repisalud.isciii.es/bitstreams/de6bfdb4-9006-43f1-80a5-9106787e9d42/download File MD5 8f5a01b5a0e53ee07b6ef7261739c713 1218313 application/pdf AssociationsOfTheMCM6-rs3754686_2016_suppl URL https://repisalud.isciii.es/bitstreams/ef4c18bf-ba13-48cd-bc1e-c7baeff39a57/download File MD5 3698edfcc45d375c66a04e0e19ead638 91854 text/plain AssociationsOfTheMCM6-rs3754686_2016.txt URL https://repisalud.isciii.es/bitstreams/f37eeffe-a2e7-4f37-94c4-21664c546b81/download File MD5 c0ccf8f516dfa8c81cc9e24920891df1 56537 text/plain AssociationsOfTheMCM6-rs3754686_2016_suppl.txt URL https://repisalud.isciii.es/bitstreams/3dae3f42-28b9-4be8-9d08-25bddbd66395/download File MD5 3698edfcc45d375c66a04e0e19ead638 91854 text/plain AssociationsOfTheMCM6-rs3754686_2016.txt URL https://repisalud.isciii.es/bitstreams/341f0f82-94a4-4f4c-af0f-f0c8c1f4cc5e/download File MD5 c0ccf8f516dfa8c81cc9e24920891df1 56537 text/plain AssociationsOfTheMCM6-rs3754686_2016_suppl.txt