title: Milk intake is not associated with low risk of diabetes or overweight-obesity: a Mendelian randomization study in 97,811 Danish individuals.
abstract: BACKGROUND
  High dairy/milk intake has been associated with a low risk of type 2 diabetes observationally, but whether this represents a causal association is unknown.
  
  
  OBJECTIVE
  We tested the hypothesis that high milk intake is associated with a low risk of type 2 diabetes and of overweight-obesity, observationally and genetically.
  
  
  METHODS
  In 97,811 individuals from the Danish general population, we examined the risk of incident type 2 diabetes and of overweight-obesity by milk intake observationally and by LCT-13910 C/T genotype [polymorphism (rs4988235) upstream from the lactase (LCT) gene], where TT and TC genotypes are associated with lactase persistence and CC with nonpersistence.
  
  
  RESULTS
  Observationally for any compared with no milk intake, the HR for type 2 diabetes was 1.10 (95% CI: 0.98, 1.24; P = 0.11), whereas the OR for overweight-obesity was 1.06 (1.02, 1.09; P = 0.002). Median milk intake was 5 glasses/wk (IQR: 0-10) for lactase TT/TC persistence and 3 (0-7) for CC nonpersistence. Genetically for lactase TT/TC persistence compared with CC nonpersistence, the OR was 0.96 (0.86, 1.08; P = 0.50) for type 2 diabetes and 1.06 (1.00, 1.12; P = 0.04) for overweight-obesity. In a stratified analysis for type 2 diabetes, corresponding values in those with and without milk intake were 0.88 (0.76, 1.03; P = 0.11) and 1.35 (1.07, 1.70; P = 0.01) (P-interaction: 0.002), whereas no gene-milk interaction on overweight-obesity was found. For a 1-glass/wk higher milk intake, the genetic risk ratio for type 2 diabetes was 0.99 (0.93, 1.06), and the corresponding observational risk was 1.01 (1.00, 1.01). For overweight-obesity, the corresponding values were 1.01 (1.00, 1.02) genetically and 1.00 (1.00, 1.01) observationally.
  
  
  CONCLUSIONS
  High milk intake is not associated with a low risk of type 2 diabetes or overweight-obesity, observationally or genetically via lactase persistence. The higher risk of type 2 diabetes in lactase-persistent individuals without milk intake likely is explained by collider stratification bias.
authors.affiliation: Department of Clinical Biochemistry, Naestved Hospital, Naestved, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Helle K M
authors.initials: HK
authors.lastname: Bergholdt
authors.affiliation: Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark; The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark;
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.affiliation: Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Research, Nykoebing Falster Hospital, Nykoebing Falster, Denmark; and Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA christina@ellervik.dk.
authors.forename: Christina
authors.initials: C
authors.lastname: Ellervik
mesh_terms: D020121:5' Untranslated Regions; D000328:Adult; D000368:Aged; D000818:Animals; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003718:Denmark / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology* / Q000235:genetics / Q000517:prevention & control; D005260:Female; D006801:Humans; D015994:Incidence; D043322:Lactase / Q000172:deficiency / Q000235:genetics; D007787:Lactose Intolerance / Q000150:complications / Q000235:genetics; D008297:Male; D057182:Mendelian Randomization Analysis; D008892:Milk / Q000009:adverse effects; D009765:Obesity / Q000150:complications / Q000453:epidemiology* / Q000235:genetics / Q000517:prevention & control; D050177:Overweight / Q000150:complications / Q000453:epidemiology* / Q000235:genetics / Q000517:prevention & control; D020641:Polymorphism, Single Nucleotide; D012042:Registries; D012306:Risk; D013223:Statistics as Topic
chemical_list: D020121:5' Untranslated Regions; D043322:Lactase
keywords: Mendelian randomization; body mass index; diabetes; lactase persistence; milk; overweight