| Summary: | 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.
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