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Association of the timing of puberty with a chromosome 2 locus.

ABSTRACT: Twin studies indicate that the timing of pubertal onset is under strong genetic control. However, genes controlling pubertal timing in the general population have not yet been identified.To facilitate the identification of genes influencing the timing of pubertal growth and maturation, we conducted linkage mapping of constitutional delay of growth and puberty (CDGP), an extreme variant of normal pubertal timing, in extended families.Fifty-two families multiply affected with CDGP were genotyped with 383 multiallelic markers. CDGP was defined based on growth charts (the age at onset of growth spurt, peak height velocity, or attaining adult height taking place at least 1.5 sd later than average). Chromosomal regions cosegregating with CDGP were identified with parametric affected-only linkage analysis using CDGP as a dichotomized trait.The genome-wide scan detected linkage of CDGP to a region on chromosome 2p13-2q13. The two-point heterogeneity LOD (HLOD) score was 1.62 (alpha = 0.27), and the corresponding multipoint HLOD was 2.54 (alpha = 0.31). Fine-mapping the region at 1 cM resolution increased the multipoint HLOD score to 4.44 (alpha = 0.41). The linkage became weaker if family members diagnosed with CDGP without growth data were also included in the analyses.The pericentromeric region of chromosome 2 harbors a gene predisposing to pubertal delay in multiply affected pedigrees. Our data suggest that this locus may be a component of the internal clock controlling the timing of the onset of puberty.

SUBMITTER: Wehkalampi K

PROVIDER: S-EPMC2685475 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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Association of the timing of puberty with a chromosome 2 locus.

Wehkalampi Karoliina K Widén Elisabeth E Laine Tiina T Palotie Aarno A Dunkel Leo L

The Journal of clinical endocrinology and metabolism 20080923 12

<h4>Context</h4>Twin studies indicate that the timing of pubertal onset is under strong genetic control. However, genes controlling pubertal timing in the general population have not yet been identified.<h4>Objective</h4>To facilitate the identification of genes influencing the timing of pubertal growth and maturation, we conducted linkage mapping of constitutional delay of growth and puberty (CDGP), an extreme variant of normal pubertal timing, in extended families.<h4>Participants and methods< ...[more]

PMID: 18812480

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Project description:BackgroundEmerging studies have investigated the association between puberty timing, particularly age at menarche (AAM), and type 2 diabetes. However, whether this association is independent of adiposity is unclear. We aimed to systematically review published evidence on the association between puberty timing and type 2 diabetes (T2D) or impaired glucose tolerance (IGT), with and without adjustment for adiposity, and to estimate the potential contribution of puberty timing to the burden of T2D in the United Kingdom (UK).Methods and findingsWe searched PubMed, Medline, and Embase databases for publications until February 2019 on the timing of any secondary sexual characteristic in boys or girls in relation to T2D/IGT. Inverse-variance-weighted random-effects meta-analysis was used to pool reported estimates, and meta-regression was used to explore sources of heterogeneity. Twenty-eight observational studies were identified. All assessed AAM in women (combined N = 1,228,306); only 1 study additionally included men. In models without adjustment for adult adiposity, T2D/IGT risk was lower per year later AAM (relative risk [RR] = 0.91, 95% CI 0.89-0.93, p < 0.001, 11 estimates, n = 833,529, I2 = 85.4%) and higher for early versus later menarche (RR = 1.39, 95% CI 1.25-1.55, p < 0.001, 23 estimates, n = 1,185,444, I2 = 87.8%). Associations were weaker but still evident in models adjusted for adiposity (AAM: RR = 0.97 per year, 95% CI 0.95-0.98, p < 0.001, 12 estimates, n = 852,268, I2 = 51.8%; early menarche: RR = 1.19, 95% CI 1.11-1.28, p < 0.001, 21 estimates, n = 890,583, I2 = 68.1%). Associations were stronger among white than Asian women, and in populations with earlier average AAM. The estimated population attributable risk of T2D in white UK women due to early menarche unadjusted and adjusted for adiposity was 12.6% (95% CI 11.0-14.3) and 5.1% (95% CI 3.6-6.7), respectively. Findings in this study are limited by residual and unmeasured confounding, and self-reported AAM.ConclusionsEarlier AAM is consistently associated with higher T2D/IGT risk, independent of adiposity. More importantly, this research has identified that a substantial proportion of T2D in women is related to early menarche, which would be expected to increase in light of global secular trends towards earlier puberty timing. These findings highlight the need to identify the underlying mechanisms linking early menarche to T2D/IGT risk.

Dataset Information

Association of the timing of puberty with a chromosome 2 locus.

Publications

Association of the timing of puberty with a chromosome 2 locus.

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