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New genes link onset of puberty, body fat in women
Elks CE. Nat Genet. 2010;doi:10.1038/ng.714.
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At least 30 new genes, several of which have been linked to BMI, homeostasis and hormonal regulation, may play a role in triggering the onset of puberty in young women.
A meta-analysis of 32 genome-wide association studies in 87,802 women of European descent identified LIN28B and 9q31.2 as the two loci most significantly associated with age at menarche. These findings were consistent with those of previous studies, researchers for the international ReproGen consortium said. However, 40 previously unidentified loci had genome-wide significant signals, with 30 surviving more rigorous correction for overall genomic control.
“Our study found genes involved in hormone regulation, cell development and other biological pathways associated with mechanisms age at menarche, which shows that the timing of puberty is controlled by a complex range of biological processes,” Joanne Murabito, MD, ScM, associate professor of medicine at Boston University School of Medicine, said in a press release.
The researchers analyzed 16 additional studies involving 14,731 women to confirm the results of their meta-analysis. These replication studies indicated that 37 loci remained associated with age at menarche and also confirmed the relationship between age at menarche and the 30 loci that survived the more stringent criteria.
Previous research linked four of the new loci with adult BMI. The BMI-increasing allele in these genes was consistently associated with earlier menarche, the researchers said. Variants of all four loci have also demonstrated a connection to childhood BMI, suggesting a relationship between childhood BMI and age at menarche.
“Several of the genes for menarche have been associated with body weight and obesity in other studies, suggesting some women may have a genetic susceptibility to weight gain and early puberty,” Murabito said in the release. “It is important to understand that these ‘genetic factors’ can be modified by changes in lifestyle. Efforts to reduce or prevent childhood obesity should in turn help reduce the early onset of puberty in girls.”
Three new loci were also found in or near genes implicated in the regulation of energy homeostasis, and another three were discovered in or near genes linked to hormonal regulation. Additionally, ingenuity pathway analysis identified the biosynthesis of coenzyme A as the most significant pathway related to age at menarche.
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