Milk intake is not associated with ischaemic heart disease in observational or Mendelian randomization analyses in 98,529 Danish adults

TY - JOUR

T1 - Milk intake is not associated with ischaemic heart disease in observational or Mendelian randomization analyses in 98,529 Danish adults

AU - Bergholdt, Helle K M

AU - Nordestgaard, Børge G

AU - Varbo, Anette

AU - Ellervik, Christina

N1 - © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

PY - 2015/5/27

Y1 - 2015/5/27

N2 - BACKGROUND: Observationally, reports on the association between milk intake and risk of ischaemic heart disease (IHD) and myocardial infarction (MI) have produced conflicting results; and no previous large-scale study using the lactase persistent/non-persistent LCT-13910 C/T genotype as a largely unconfounded proxy for milk intake free of reverse causation has been conducted. We tested the hypothesis that milk intake observationally and genetically through the LCT-13910 C/T genotype is associated with risk of IHD and MI in a Mendelian randomization design.METHODS: We included 98,529 White individuals of Danish descent, aged 20-100 years, from three studies of the general population. Information on IHD (N = 10,372) and MI (N = 4188) were obtained from national Danish registries. First, we investigated observational associations between milk intake and incident IHD and MI. Second, we confirmed the association between the rs4988235 genetic variant LCT-13910 C/T, associated with lactase persistence/non-persistence, and milk intake. Finally, we tested whether LCT-13910 C/T genotype was associated with risk of IHD and MI as well as with cardiovascular risk factors.RESULTS: During a mean follow-up time of 5.4 years, the observational hazard ratio for a 1 glass/week higher milk intake was 1.00 [95% confidence interval (CI): 1.00,1.01] for both IHD and MI. Median milk intake was 3 glasses/week (interquartile range: 0-7) in lactase CC non-persistent individuals compared with 5 glasses/week (0-10) in lactase TC/TT persistent individuals (P = 3*10(-60)). In the dominant genetic model comparing lactase TC/TT persistent individuals with lactase CC non-persistent individuals, the odds ratio was 1.00 (0.92,1.09) for IHD and 0.96 (0.84,1.09) for MI. Finally, in the dominant genetic model genotype was not associated convincingly with plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides or glucose, nor with blood pressure.CONCLUSION: Milk intake was not associated with risk of IHD or MI, observationally or genetically.

AB - BACKGROUND: Observationally, reports on the association between milk intake and risk of ischaemic heart disease (IHD) and myocardial infarction (MI) have produced conflicting results; and no previous large-scale study using the lactase persistent/non-persistent LCT-13910 C/T genotype as a largely unconfounded proxy for milk intake free of reverse causation has been conducted. We tested the hypothesis that milk intake observationally and genetically through the LCT-13910 C/T genotype is associated with risk of IHD and MI in a Mendelian randomization design.METHODS: We included 98,529 White individuals of Danish descent, aged 20-100 years, from three studies of the general population. Information on IHD (N = 10,372) and MI (N = 4188) were obtained from national Danish registries. First, we investigated observational associations between milk intake and incident IHD and MI. Second, we confirmed the association between the rs4988235 genetic variant LCT-13910 C/T, associated with lactase persistence/non-persistence, and milk intake. Finally, we tested whether LCT-13910 C/T genotype was associated with risk of IHD and MI as well as with cardiovascular risk factors.RESULTS: During a mean follow-up time of 5.4 years, the observational hazard ratio for a 1 glass/week higher milk intake was 1.00 [95% confidence interval (CI): 1.00,1.01] for both IHD and MI. Median milk intake was 3 glasses/week (interquartile range: 0-7) in lactase CC non-persistent individuals compared with 5 glasses/week (0-10) in lactase TC/TT persistent individuals (P = 3*10(-60)). In the dominant genetic model comparing lactase TC/TT persistent individuals with lactase CC non-persistent individuals, the odds ratio was 1.00 (0.92,1.09) for IHD and 0.96 (0.84,1.09) for MI. Finally, in the dominant genetic model genotype was not associated convincingly with plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides or glucose, nor with blood pressure.CONCLUSION: Milk intake was not associated with risk of IHD or MI, observationally or genetically.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Animals

KW - Denmark

KW - Female

KW - Genotype

KW - Humans

KW - Lactase

KW - Male

KW - Mendelian Randomization Analysis

KW - Middle Aged

KW - Milk

KW - Myocardial Infarction

KW - Myocardial Ischemia

KW - Risk Factors

KW - Young Adult

U2 - 10.1093/ije/dyv109

DO - 10.1093/ije/dyv109

M3 - Journal article

C2 - 26085675

SN - 0300-5771

VL - 44

SP - 587

EP - 603

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

IS - 2

ER -