Mendelian randomisation study of childhood BMI and early menarche

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/ m 2 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. © 2011 hannah s. mumby et al.