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首页> 外文期刊>International Journal of Obesity >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
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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

机译：使用两种样本的孟德尔随机化分析在高达1,904,220个个人之间使用两样孟德尔随机性分析

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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. 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). 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). 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.
机译：高奶入摄入量与心脏代谢风险有关。我们进行了孟德尔随机化（MR）研究，以获得使用乳糖酶持久性（LCT-13910 C> T，RS4988235）变体作为乐器变量的乳酸消耗和心脏代谢性状的因果关系的证据。我们测试了LCT基因型与牛奶消耗（用于验证）和心脏代谢性状（用于可能的因果关系）的关联，从基于三个大规模的人口的研究中的数据分析（1958年英国出生队列，健康和退休研究，以及英国Biobank）高达417,236名参与者，并在中间特征上使用Consortia Meta分析的总结统计数据（n = 123,665-697,307）并扩展到涵盖疾病终点（n = 86,995-149,821）。在英国Biobank中，LCT变体的“T”等位基因的载体更可能消耗牛奶（P = 7.02 10 14）。在包括英国Biobank的Meta分析中，1958Ab，基于HRS和基于联盟的研究，在添加剂模型下，'T'等位基因与更高的体重指数（BMI）相关（Pmeta-Analysis = 4.68 10 12）和更低总胆固醇（TC）（P = 2.40 10 36），低密度脂蛋白胆固醇（LDL-C）（P = 2.08 10 26）和高密度脂蛋白胆固醇（HDL-C）（P = 9.40 10 13）。在结束间分析中，冠状动脉疾病的风险较低（或：0.86,95％CI：0.75-0.99），但不含2型糖尿病（或：1.06,95％CI：0.97- 1.16）。此外，两个样本MR分析显示出遗传仪表化乳摄入和更高的BMI之间的因果关系（P = 3.60 10 5）和体脂肪（总体脂肪，腿脂，手臂脂肪和躯干脂肪; P <1.37 10 6）和下LDL-C（P = 3.60 10 6），TC（P = 1.90 10 6）和HDL-C（P = 3.00 10 5）。我们的大型MR研究为牛奶消费与较高的BMI但血清胆固醇水平降低的遗传证据提供了遗传证据。这些数据表明无需限制牛奶摄入量的心血管疾病风险，并提出了在进一步研究中确认确认的建议益处。

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