title: Mendelian Randomisation Study of Childhood BMI and Early Menarche.
abstract: 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.
authors.affiliation: MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, P.O. Box 285, Cambridge CB2 0QQ, UK.
authors.forename: Hannah S
authors.initials: HS
authors.lastname: Mumby
authors.forename: Cathy E
authors.initials: CE
authors.lastname: Elks
authors.forename: Shengxu
authors.initials: S
authors.lastname: Li
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Sharp
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Robert N
authors.initials: RN
authors.lastname: Luben
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Ruth J F
authors.initials: RJ
authors.lastname: Loos
authors.forename: Ken K
authors.initials: KK
authors.lastname: Ong