TY - JOUR

T1 - Lactase persistence, milk intake, and mortality in the Danish general population

T2 - a Mendelian randomization study

AU - Bergholdt, Helle Kirstine Mørup

AU - Nordestgaard, Børge Grønne

AU - Varbo, Anette

AU - Ellervik, Christina

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Meta-analyses have suggested no association between milk intake and mortality. Since only few studies have been conducted, we investigated the association between the lactase persistent genetic variant LCT-13910 C/T (rs4988235), a proxy for long-term low and high intake of milk, and mortality. We used two Danish population-based studies with self-reported intake of milk and genotyping for LCT-13910 C/T. We obtained information on all-cause and cause-specific mortality (cardiovascular and cancer) from the national Danish registries. We used multivariable adjusted Cox regression to assess the association between milk intake and mortality in 74,241 individuals, and both logistic and Cox-regression to assess the association between genetic lactase persistence and mortality in 82,964 individuals using a Mendelian randomization design. We applied per T-allele, co-dominant and dominant models. During a mean follow-up of 7 years, 9759 individuals died, 2166 from cardiovascular disease, and 2822 from cancer. Observationally, there was no association between intake of skimmed milk and all-cause or cardiovascular mortality, and we did not find any associations between intake of semi-skimmed or whole milk with all-cause or cause-specific mortality. Intake of skimmed milk was associated with lower cancer mortality with a hazard ratio of 0.97 (95% CI 0.96–1.00) per doubling in milk intake. Per T-allele, milk intake increased with 0.58 (0.50–0.68) glasses/week. Genetically, we found no associations between the lactase persistent LCT-13910 C/T genotype and all-cause or cause-specific mortality; per T-allele OR (95% CI) for all-cause mortality was 1.02 (0.97–1.06). Our study did not provide strong evidence of observational or genetic associations between milk intake and all-cause or cause-specific mortality.

AB - Meta-analyses have suggested no association between milk intake and mortality. Since only few studies have been conducted, we investigated the association between the lactase persistent genetic variant LCT-13910 C/T (rs4988235), a proxy for long-term low and high intake of milk, and mortality. We used two Danish population-based studies with self-reported intake of milk and genotyping for LCT-13910 C/T. We obtained information on all-cause and cause-specific mortality (cardiovascular and cancer) from the national Danish registries. We used multivariable adjusted Cox regression to assess the association between milk intake and mortality in 74,241 individuals, and both logistic and Cox-regression to assess the association between genetic lactase persistence and mortality in 82,964 individuals using a Mendelian randomization design. We applied per T-allele, co-dominant and dominant models. During a mean follow-up of 7 years, 9759 individuals died, 2166 from cardiovascular disease, and 2822 from cancer. Observationally, there was no association between intake of skimmed milk and all-cause or cardiovascular mortality, and we did not find any associations between intake of semi-skimmed or whole milk with all-cause or cause-specific mortality. Intake of skimmed milk was associated with lower cancer mortality with a hazard ratio of 0.97 (95% CI 0.96–1.00) per doubling in milk intake. Per T-allele, milk intake increased with 0.58 (0.50–0.68) glasses/week. Genetically, we found no associations between the lactase persistent LCT-13910 C/T genotype and all-cause or cause-specific mortality; per T-allele OR (95% CI) for all-cause mortality was 1.02 (0.97–1.06). Our study did not provide strong evidence of observational or genetic associations between milk intake and all-cause or cause-specific mortality.

KW - Dairy

KW - Lactase persistence

KW - Lactose

KW - LCT-13910

KW - Milk

KW - Mortality

U2 - 10.1007/s10654-017-0328-x

DO - 10.1007/s10654-017-0328-x

M3 - Journal article

C2 - 29071499

AN - SCOPUS:85032215500

VL - 33

SP - 171

EP - 181

JO - European Journal of Epidemiology

JF - European Journal of Epidemiology

SN - 0393-2990

IS - 2

ER -