title: Association of lactase persistence genotype with milk consumption, obesity and blood pressure: a Mendelian randomization study in the 1982 Pelotas (Brazil) Birth Cohort, with a systematic review and meta-analysis.
abstract: Milk intake has been associated with lower blood pressure (BP) in observational studies, and randomized controlled trials suggested that milk-derived tripeptides have BP-lowering effects. Milk intake has also been associated with body mass index (BMI). Nevertheless, it is unclear whether increasing milk consumption would reduce BP in the general population.
  
  
  
  We investigated the association of milk intake with obesity and BP using genetically-defined lactase persistence (LP) based on the rs4988235 polymorphism in a Mendelian randomization design in the 1982 Pelotas (Southern Brazil) Birth Cohort. These results were combined with published reports identified through a systematic review using meta-analysis.
  
  
  
  In the 1982 Pelotas Birth Cohort, milk intake was 42 [95% confidence interval (CI): 18; 67) ml/day higher in LP individuals. In conventional observational analysis, each 1-dl/day increase in milk intake was associated with -0.26 (95% CI: -0.33; -0.19) kg/m2in BMI and -0.31 (95% CI: -0.46; -0.16) and -0.35 (95% CI: -0.46; -0.23) mmHg in systolic and diastolic BP, respectively. These results were not corroborated when analysing LP status, but confidence intervals were large. In random effects meta-analysis, LP individuals presented higher BMI [0.17 (95% CI: 0.07; 0.27) kg/m2] and higher odds of overweight-obesity [1.09 (95% CI: 1.02; 1.17)]. There were no reliable associations for BP.
  
  
  
  Our study supports that LP is positively associated with obesity, suggesting that the negative association of milk intake with obesity is likely due to limitations of conventional observational studies. Our findings also do not support that increased milk intake leads to lower BP.
authors.affiliation: Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil fernandophartwig@gmail.com.
authors.forename: Fernando Pires
authors.initials: FP
authors.lastname: Hartwig
authors.affiliation: Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
authors.forename: Bernardo Lessa
authors.initials: BL
authors.lastname: Horta
authors.affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.affiliation: Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
authors.forename: Christian Loret
authors.initials: CL
authors.lastname: de Mola
authors.affiliation: Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
authors.forename: Cesar Gomes
authors.initials: CG
authors.lastname: Victora
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001795:Blood Pressure Determination; D015992:Body Mass Index; D001938:Brazil; D004032:Diet; D005838:Genotype; D006801:Humans; D043322:Lactase / Q000235:genetics* / Q000378:metabolism; D057182:Mendelian Randomization Analysis; D008892:Milk; D009765:Obesity / Q000453:epidemiology*; D064887:Observational Studies as Topic; D020641:Polymorphism, Single Nucleotide; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
chemical_list: D043322:Lactase
keywords: Lactase persistence; Mendelian randomization; blood pressure; body mass index; milk; obesity