Genetic loci associated with age at menopause and bone mineral density in Southern Chinese women: a replication study Abstract

Hang Wun Raymond LI1, Ching Lung CHEUNG2,3,4, Kathryn Choon Beng TAN2, Pak Chung SHAM3, Annie Wai Chee KUNG2, Grace Wai King TANG1
 
The first two authors contributed equally to this manuscript
 
1 Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, Hong Kong
2 Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
3 Centre for Genomic Sciences, The University of Hong Kong, Hong Kong
4 Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong

Purpose: A meta-analysis of genome-wide association studies in Europeans identified 19 loci associated with age at menopause. This study aimed to validate these loci in Southern Chinese women and their association with bone mineral density.
Methods: This was a replication study on 609 women who had participated in the Hong Kong Osteoporosis Study. Archived DNA was genotyped using the Sequenom iPLEX platform. 14 single-nucleotide polymorphisms that had been reported to be associated with age at menopause or bone mineral density in European populations were examined using univariate linear and logistic regression analyses.
Results: Of the 14 genotyped loci, only rs11668344, rs365132, and rs10183486 were associated with age
at menopause in Southern Chinese women, with effect sizes of -0.847 (p=0.014), 0.524 (p=0.008), and -1.300 (p=0.028), respectively. Two of them (rs11668344 and rs365132) were associated with early menopause, with the odds ratio being 1.975 (p=0.048) and 0.639 (p=0.032), respectively. Each unit increase in the genetic risk score composed of these two single nucleotide polymorphisms was associated with an odds ratio of 1.62 (p=0.006) for early menopause. rs10183486 was also associated with bone mineral density at the lumbar spine (p=0.048) and femoral neck (p=0.039).
Conclusions: rs11668344, rs365132, and rs10183486 are associated with age at menopause and bone mineral density in Southern Chinese women.

Hong Kong J Gynaecol Obstet Midwifery 2019; 19(1):44–8
 
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