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

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obesity 111 International Journal of EpidemiologyAssociation of lactase persistence genotype with milk consumption, obesity and blood pressure: a Mendelian randomization study in the 1982 Pelotas (Brazil) Birth Cohort, with
obesity 1055 would reduce BP in the general population.Methods: 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
obesity 1992 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.Conclusions: Our study supports
obesity 2142 reliable associations for BP.Conclusions: 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
obesity 2212 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
obesity 2622 more pronounced among individuals of more European ancestry.Milk intake was negatively associated with obesity and blood pressure in conventional observational analysis in the 1982 Pelotas Birth Cohort.LP was positively
obesity 2774 observational analysis in the 1982 Pelotas Birth Cohort.LP was positively associated with BMI and overweight- obesity in our meta-analysis which was based on a systematic literature review.There were no reliable meta-analytical
obesity 5858 individuals identified a positive association between intake of any type of milk and risk of overweight- obesity ; however, there was no dose-response relationship, and the association was observed for fat-free, but
obesity 6743 overall dietary patterns. Therefore, the direction of the association (if any) of milk intake with obesity is unclear.The use of genetic variants as proxies of modifiable exposures can improve causal inference
obesity 7804 consumption. However, the aforementioned large Danish study did not detect strong associations with obesity and blood pressure.[30],[37]In the present study, we evaluated whether genetically-defined LP is associated
obesity 7938 pressure.[30],[37]In the present study, we evaluated whether genetically-defined LP is associated with milk intake, obesity and blood pressure among subjects who have been followed up since birth in a southern Brazilian city.
obesity 10226 2012–13 follow-up (when individuals were 30–31 years of age).Outcome variables were: BMI, overweight- obesity , systolic blood pressure, diastolic blood pressure and raised blood pressure. For BMI (kg/m2), weight
obesity 10471 portable weighing devices and stadiometers of 100 g and 1 cm of precision, respectively. Overweight- obesity was defined as BMI ≥ 25 kg/m2. Systolic and diastolic blood pressures were measured in mmHg
obesity 13121 review and meta-analysisA systematic review of the literature regarding the association of LP with obesity and blood pressure was performed through Ovid [https://ovidsp.tx.ovid.com/] which allows simultaneously
obesity 13965 association of the rs4988235 variant (exposure) with the following outcomes: BMI (continuous), overweight- obesity (binary), systolic and diastolic blood pressure (continuous) and raised blood pressure/hypertension
obesity 14828 (e.g. controls and cases, respectively, in a case-control study)];cut-off used to determine overweight- obesity or raised blood pressure/hypertension;covariates adjusted for in multivariable models. After data extraction,
obesity 20537 birthweight. Compared with the 2012–13 follow-up, studied subjects presented higher prevalence of obesity (BMI ≥ 30 kg/m2).In general, dairy consumption was positively associated with socioeconomic
obesity 24839 ≥ 85%.bIndividuals with European genomic ancestry < 85%.Milk intake was inversely associated with obesity and blood pressure (Table 2). After controlling for sociodemographic variables (which did not substantially
obesity 25282 as well as with odds ratio of 0.93 (95% CI: 0.91; 0.96) and 0.93 (95% CI: 0.90; 0.96) for overweight- obesity and raised blood pressure, respectively. There were no reliable associations supporting effect modification
obesity 25925 (kg/m2)N27612595P1.5 × 10−133.2 × 10−13β (95% CI)−0.25 (−0.32; −0.18)−0.26 (−0.33; −0.19)Overweight- obesity bN27612595P1.8 × 10−77.2 × 10−8OR (95% CI)0.94 (0.91; 0.96)0.93 (0.91; 0.96)Systolic BP
obesity 27026 association of genetically-defined LP with potential confounders of the association of milk intake with obesity and/or blood pressure. In unadjusted analyses, LP individuals had 0.4 (95% CI: 0.1; 0.7) more complete
obesity 27899 1.6) g/day more among milk drinkers.There were no strong associations of genetically defined LP with obesity or blood pressure (Table 3), although there was some indication for BMI. In unadjusted models, BMI was
obesity 28266 0.88). These results were directionally consistent with the point odds ratio estimate for overweight- obesity [1.09 (95% CI: 0.93; 1.28)]. Moreover, point estimates of both outcomes were directionally consistent
obesity 29717 (kg/m2)Pinteraction = 0.467N2782278014271353P0.2070.0520.3840.074β (95% CI)0.27 (−0.15; 0.69)0.44 (0.00; 0.88)0.26 (−0.33; 0.86)0.60 (−0.06; 1.25)Overweight- obesity cPinteraction = 0.612N2782278014271353P0.5650.2940.7990.259OR (95% CI)1.05 (0.90; 1.22)1.09 (0.93;
obesity 30677 meta-analytical linear regression coefficient (β) or odds ratio (OR) estimates of BMI, overweight- obesity , systolic, diastolic and raised blood pressure, according to genetically defined LP (reference group:
obesity 30836 according to genetically defined LP (reference group: non-LP individuals)OutcomeBMI (kg/m2)aOverweight- obesity bSystolic BP (mmHg)aDiastolic BP(mmHg)aRaised BPbNumber ofEstimates145774Individuals142864102640112440112442101507HeterogeneityI2
obesity 32448 0.17 (95% CI: 0.07; 0.27) kg/m2 higher in LP individuals, and the pooled odds ratio for overweight- obesity was 1.09 (95% CI: 1.02; 1.17). Results for diastolic blood pressure were also suggestive of a positive
obesity 33143 ranged from 0.08 to 0.20 and none of the 95% confidence intervals included zero. Regarding overweight- obesity , the odds ratio estimates ranged from 0.07 to 1.15 and only in one case the 95% confidence intervals
obesity 38295 Brazil. In conventional observational analysis, there was an inverse association of milk intake with obesity and blood pressure. However, Mendelian randomization analyses based on genetically defined LP did not
obesity 38496 did not confirm these associations. Moreover, LP was positively associated with BMI and overweight- obesity in our meta-analysis.The aforementioned meta-analysis[36] had already detected that LP individuals have
obesity 38963 study on 97 811 Danish individuals failed to detect strong associations of LP with BMI and overweight- obesity .[30] Our findings confirmed the previously reported positive association of LP with BMI, which was corroborated
obesity 39117 reported positive association of LP with BMI, which was corroborated by an association with overweight- obesity in the same direction. Although the sample size of the Danish study represented 64% and 95% of the pooled
obesity 39267 size of the Danish study represented 64% and 95% of the pooled sample sizes for BMI and overweight- obesity (respectively), its actual weight in the meta-analysis is lower due to the very low prevalence of lactase
obesity 39736 consistent. In additional analyses performed using fixed effects, the pooled estimates for BMI and overweight obesity were 0.08 (95% CI: 0.05; 0.11) and 1.09 (1.02; 1.17), respectively, corroborating the findings obtained
obesity 39954 random effects. These findings suggest a positive causal effect of milk intake on BMI and overweight- obesity , suggesting that the negative associations observed in conventional observational analysis were due
obesity 46767 aforementioned Danish studies did not detect reliable LP-milk intake interactions regarding overweight- obesity [30] or blood pressure. However, such interactions were detected regarding sex (likely explained by collider
obesity 52352 in ml/day comparing LP and non-LP individuals) across studies (as mentioned above).Considering that obesity and elevated blood pressure are important risk factors for cardiovascular diseases, identifying their
obesity 52778 increasing milk intake in the target population would likely increase its BMI and prevalence of overweight- obesity and, at best, not influence blood pressure. Our findings are in accordance with the notion that the

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