Mendelian Randomisation Study of Childhood BMI and Early Menarche.
Mendelian Randomisation Study of Childhood BMI and Early Menarche.
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Mendelian童年BMI和初潮的孟德尔随机化研究。
DOI：
10.1155/2011/180729
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发表时间：
2011
影响因子：
3.3
通讯作者：
Ong KK
中科院分区：
文献类型：
--
作者：
Mumby HS;Elks CE;Li S;Sharp SJ;Khaw KT;Luben RN;Wareham NJ;Loos RJ;Ong KK
为了推断儿童期BMI与初月经年龄之间的因果关系，我们使用12个已确定的“BMI增加”遗传变异作为较高BMI的工具变量（IV）进行了孟德尔随机化分析。在来自EPIC-Norfolk队列的8156名欧洲血统女性中，身高在39-77岁之间测量；初潮时的年龄和20岁时的体重都是自我回忆的，20岁时的体重指数被计算为童年体重指数的代表。对12个与bmi相关的常见变异（FTO、MC4R、TMEM18、GNPDA2、KCTD15、NEGR1、BDNF、ETV5、MTCH2、SEC16B、FAIM2和SH2B1）进行DNA基因分型，并通过将所有12个位点上的bmi增加等位基因数量相加，计算每个个体的“bmi增加等位基因得分”。使用BMI增加等位基因评分作为BMI的工具变量，儿童BMI每增加1 kg/m2，预计会导致6.5% （95% CI: 4.6-8.5%）的早期月经初露（12岁之前）的绝对风险增加。虽然孟德尔随机化分析依赖于许多假设，但我们的研究结果支持BMI对早期月经初潮的因果影响，并表明儿童肥胖的患病率增加将导致早期月经初潮的患病率呈类似趋势。
To infer the causal association between childhood BMI and age at menarche, we performed a mendelian randomisation analysis using twelve established “BMI-increasing” genetic variants as an instrumental variable (IV) for higher BMI. In 8,156 women of European descent from the EPIC-Norfolk cohort, height was measured at age 39–77 years; age at menarche was self-recalled, as was body weight at age 20 years, and BMI at 20 was calculated as a proxy for childhood BMI. DNA was genotyped for twelve BMI-associated common variants (in/near FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, ETV5, MTCH2, SEC16B, FAIM2 and SH2B1), and for each individual a “BMI-increasing-allele-score” was calculated by summing the number of BMI-increasing alleles across all 12 loci. Using this BMI-increasing-allele-score as an instrumental variable for BMI, each 1 kg/m2 increase in childhood BMI was predicted to result in a 6.5% (95% CI: 4.6–8.5%) higher absolute risk of early menarche (before age 12 years). While mendelian randomisation analysis is dependent on a number of assumptions, our findings support a causal effect of BMI on early menarche and suggests that increasing prevalence of childhood obesity will lead to similar trends in the prevalence of early menarche.