No abstract

Reproductive Toxicology 24 (2007) 131-138. doi:10.1016/j.reprotox.2007.07.005Received by publisher: 2007-06-08Harvest Date: 2016-01-04 12:22:51DOI: 10.1016/j.reprotox.2007.07.005Page Range: 131-13

We found a significant positive association of repeat size with ovarian dysfunction, but have preliminary evidence that this relationship is non-linear. We suggest that FMR1 repeat size in the lower range (<80 repeats) contributes to the variation in age at menopause; thus, FMR1 could be considered a quantitative trait locus. More importantly, when repeat size exceeds this threshold, the increase in risk for ovarian dysfunction is clinically significant. Intriguingly, this risk appears to plateau, or perhaps decrease, among women with very high repeats (> or =100 repeats).

H/A and N/S MSS and MSD were common among computer users. More than 50% of computer users reported MSS during the first year after starting a new job.

The timing of puberty is highly variable1. We carried out a genome-wide association study for age at menarche in 4,714 women and report an association in LIN28B on chromosome 6 (rs314276, minor allele frequency (MAF) = 0.33, P = 1.5 × 10 −8 ). In independent replication studies in 16,373 women, each major allele was associated with 0.12 years earlier menarche (95% CI = 0.08-0.16; P = 2.8 × 10 −10 ; combined P = 3.6 × 10 −16 ). This allele was also associated with earlier breast development in girls (P = 0.001; N = 4,271); earlier voice breaking (P = 0.006, N = 1,026) and more advanced pubic hair development in boys (P = 0.01; N = 4,588); a faster tempo of height growth in girls (P = 0.00008; N = 4,271) and boys (P = 0.03; N = 4,588); and shorter adult height in women (P = 3.6 × 10 −7 ; N = 17,274) and men (P = 0.006; N = 9,840) in keeping with earlier growth cessation. These studies identify variation in LIN28B, a potent and specific regulator of microRNA processing2, as the first genetic determinant regulating the timing of human pubertal growth and development.Puberty, the transition from childhood to adult body size and sexual maturity, is a complex multistaged process involving growth acceleration, weight gain and the appearance of secondary sexual physical features over a 2-to 3-year period1. Early onset and progression of puberty is seen in some overweight and obese children. In addition to its psycho-social and public health implications, early puberty is associated with increased long-term risk for diseases including obesity, diabetes and cancer3. The stages of puberty and their transitions are difficult to measure accurately1. Epidemiological studies often use age at menarche, the onset of the first menstrual period in girls, to indicate the timing of puberty, as this distinct event is often well recalled many years later1. Girls with earlier menarche are heavier and taller than other girls during childhood; they remain heavier but are shorter as adults3, reflecting their earlier cessation of growth. Twins studies estimate that 44-95% of the variance in age at menarche may be heritable1. However, specific common genetic variants that influence the timing of puberty have not yet been convincingly demonstrated4.To identify common variants associated with the timing of puberty, we conducted a genome-wide association (GWA) study for age at menarche in 4,714 women from two general population studies and one obese case study using the same Affymetrix GeneChip 500K array (Supplementary Note online). Only one SNP, rs314276 in intron 2 of LIN28B on chromosome 6 (MAF 0.33), reached genome-wide statistical significance (P = 1.5 × 10 −8 , Supplementary Fig. 1 online). In these GWA studies overall each major C allele at rs314276 was associated with a mean 0.22 years (95% CI = 0.14-0.29) earlier age at menarche. SNP rs314276 lies in a region of high linkage disequilibrium (LD); although no other SNPs in this region were directly genotyped in these arrays, imputation to HapMap build 35 revealed a further 11 SN...