scholarly journals Causal link between milk consumption and obesity? A 10-year longitudinal study and a Mendelian randomization study

2021 ◽  
Author(s):  
Kuang-Mao Chiang ◽  
Wen-Harn Pan
Keyword(s):  
Longitudinal Study ◽  
Weight Status ◽  
Mendelian Randomization ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Energy Restriction ◽  
Milk Intake ◽  
Milk Consumption ◽  
Lower Odds ◽  
Mr Study

Background: Obesity control and prevention remains challenging. Randomized controlled trials in western countries have demonstrated efficacy of dairy supplementation on fat mass reduction and lean mass increase, when combined with energy restriction protocols. However, there is scanty information on this issue among the East Asian population. Objective: The aim of this study is to investigate the association between milk consumption and weight status in Asian. Design: First, we studied the association between milk intake and body mass index (BMI) changes in a 10-year longitudinal study of Cardiovascular Disease Risk Factor Two-township Study (CVDFACTS) with 1,644 adults. Second, taking advantage of the genetic and phenotype data of 10,000 participants collected by Taiwan Biobank (TWB), we carried out a Mendelian randomization (MR) study to investigate the causal relationship between milk intake and BMI. A lactase persistence genetic marker (rs4954490) was used as the instrumental variable. Results: We found in the longitudinal study that higher baseline milk consumption level was associated with lower odds of increasing BMI or maintaining overweight/obesity status. In the MR study, we found that G allele of the rs4954490, a surrogate of greater milk intake, was associated with lower odds of being obese (BMI > 27 kg/m2); the odds ratio (OR) for the GG versus AA is 0.85 (P = 0.037), and the OR for the GA versus AA is 0.84 (P = 0.032). Conclusions: These findings support current food guide in Asian countries to include dairy group as one of the six food groups for nutrition recommendation.

scholarly journals Evidence for a causal association between milk intake and cardiometabolic disease outcomes using a two-sample Mendelian Randomization analysis in up to 1,904,220 individuals

2021 ◽  
Author(s):  
Karani Santhanakrishnan Vimaleswaran ◽  
Ang Zhou ◽  
Alana Cavadino ◽  
Elina Hyppönen
Keyword(s):  
Large Scale ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Density Lipoprotein ◽  
Milk Intake ◽  
Milk Consumption ◽  
Causal Association ◽  
Uk Biobank ◽  
Meta Analyses ◽  
Mr Study

Abstract Background High milk intake has been associated with cardio-metabolic risk. We conducted a Mendelian Randomization (MR) study to obtain evidence for the causal relationship between milk consumption and cardio-metabolic traits using the lactase persistence (LCT-13910 C > T, rs4988235) variant as an instrumental variable. Methods We tested the association of LCT genotype with milk consumption (for validation) and with cardio-metabolic traits (for a possible causal association) in a meta-analysis of the data from three large-scale population-based studies (1958 British Birth Cohort, Health and Retirement study, and UK Biobank) with up to 417,236 participants and using summary statistics from consortia meta-analyses on intermediate traits (N = 123,665–697,307) and extended to cover disease endpoints (N = 86,995–149,821). Results In the UK Biobank, carriers of ‘T’ allele of LCT variant were more likely to consume milk (P = 7.02 × 10−14). In meta-analysis including UK Biobank, the 1958BC, the HRS, and consortia-based studies, under an additive model, ‘T’ allele was associated with higher body mass index (BMI) (Pmeta-analysis = 4.68 × 10−12) and lower total cholesterol (TC) (P = 2.40 × 10−36), low-density lipoprotein cholesterol (LDL-C) (P = 2.08 × 10−26) and high-density lipoprotein cholesterol (HDL-C) (P = 9.40 × 10−13). In consortia meta-analyses, ‘T’ allele was associated with a lower risk of coronary artery disease (OR:0.86, 95% CI:0.75–0.99) but not with type 2 diabetes (OR:1.06, 95% CI:0.97–1.16). Furthermore, the two-sample MR analysis showed a causal association between genetically instrumented milk intake and higher BMI (P = 3.60 × 10−5) and body fat (total body fat, leg fat, arm fat and trunk fat; P < 1.37 × 10−6) and lower LDL-C (P = 3.60 × 10−6), TC (P = 1.90 × 10−6) and HDL-C (P = 3.00 × 10−5). Conclusions Our large-scale MR study provides genetic evidence for the association of milk consumption with higher BMI but lower serum cholesterol levels. These data suggest no need to limit milk intakes with respect to cardiovascular disease risk, with the suggested benefits requiring confirmation in further studies.

scholarly journals Physical activity, sedentary behavior and risk of coronary artery disease, myocardial infarction and ischemic stroke: a two-sample Mendelian randomization study

2021 ◽  
Author(s):  
Martin Bahls ◽  
Michael F. Leitzmann ◽  
André Karch ◽  
Alexander Teumer ◽  
Marcus Dörr ◽  
...  
Keyword(s):  
Physical Activity ◽  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Ischemic Stroke ◽  
Coronary Artery ◽  
Sedentary Behavior ◽  
Mendelian Randomization ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Artery Disease

Abstract Aims Observational evidence suggests that physical activity (PA) is inversely and sedentarism positively related with cardiovascular disease risk. We performed a two-sample Mendelian randomization (MR) analysis to examine whether genetically predicted PA and sedentary behavior are related to coronary artery disease, myocardial infarction, and ischemic stroke. Methods and results We used single nucleotide polymorphisms (SNPs) associated with self-reported moderate to vigorous PA (n = 17), accelerometer based PA (n = 7) and accelerometer fraction of accelerations > 425 milli-gravities (n = 7) as well as sedentary behavior (n = 6) in the UK Biobank as instrumental variables in a two sample MR approach to assess whether these exposures are related to coronary artery disease and myocardial infarction in the CARDIoGRAMplusC4D genome-wide association study (GWAS) or ischemic stroke in the MEGASTROKE GWAS. The study population included 42,096 cases of coronary artery disease (99,121 controls), 27,509 cases of myocardial infarction (99,121 controls), and 34,217 cases of ischemic stroke (404,630 controls). We found no associations between genetically predicted self-reported moderate to vigorous PA, accelerometer-based PA or accelerometer fraction of accelerations > 425 milli-gravities as well as sedentary behavior with coronary artery disease, myocardial infarction, and ischemic stroke. Conclusions These results do not support a causal relationship between PA and sedentary behavior with risk of coronary artery disease, myocardial infarction, and ischemic stroke. Hence, previous observational studies may have been biased. Graphic abstract

scholarly journals Milk intake and incident stroke and coronary heart disease in populations of European descent: A Mendelian Randomization study

2021 ◽  
pp. 1-25
Author(s):  
L.E.T. Vissers ◽  
I. Sluijs ◽  
S. Burgess ◽  
N.G. Forouhi ◽  
H. Freisling ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Mendelian Randomization ◽  
Cox Regression ◽  
Milk Intake ◽  
Outcome Analysis ◽  
Milk Consumption ◽  
Uk Biobank ◽  
Chd Risk ◽  
Residual Confounding

Abstract Higher milk intake has been associated with a lower stroke risk, but not with risk of coronary heart disease (CHD). Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29,328 participants (4,611 stroke; 9,828 CHD) of the EPIC-CVD (8 European countries) and EPIC-NL case-cohort studies. rs4988235, a lactase persistence (LP) single nucleotide polymorphism which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777,024 participants (50,804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483,966 participants (61,612 cases) from CARDIoGRAM, UK Biobank and EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (β=13.7 g/day; 95%CI: 8.4-19.1) and EPIC-NL (36.8 g/day; 20.0-53.5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/day 1.05; 95%CI: 0.94-1.16) or CHD (1.02; 0.96-1.08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (odds ratios 1.02; 0.99-1.05) or CHD (0.99; 0.95-1.03). Current Mendelian Randomization analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.

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