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KMID : 0381120130350010069
Genes and Genomics
2013 Volume.35 No. 1 p.69 ~ p.75
Replication of genomewide association studies on age at menarche in the Korean population
Hong Kyung-Won

Kim Cheong-Sik
Min Hae-Sook
Park Seon-Joo
Park Jae-Kyung
Ahn Youn-Jhin
Kim Sung-Soon
Kim Yeon-Jung
Abstract
Early menarche is associated with adverse health outcomes, including breast cancer, endometrial cancer, obesity, type 2 diabetes, and cardiovascular disease. Recently, a genomewide association study (GWAS) of age at menarche (AAM) in 104,533 individuals of European ancestry was reported by the ReproGen consortium. They identified 42 loci known and novel loci that were linked to age at menarche. Because age at menarche varies between ethnic groups, we decided to investigate if these results would be replicated in the Korean population. To this end, we examined the association of the SNPs reported in the ReproGen GWAS with AAM in 3,194 individuals from the Korean Genome and Epidemiology Study (KoGES) cohort. Genotype data for total 17 SNPs (6 genotyped SNPs and 11 imputed SNPs) were available for the association analysis using linear regression analysis for age at menarche with controlling current age, waist-to-hip ratio, and body mass index as the covariates. We found replication of the ReproGen study in two SNPs; one SNP (rs466639) in the retinoic acid receptor gamma gene (RXRG), showing a significant association with early menarche (beta = ?0.224 ¡¾ 0.065, p value = 5.2 ¡¿ 10?4, Bonferroni-corrected p value = 0.009), and the other (rs10899489), in GRB2 (growth factor receptor bound protein 2)-associated binding protein 2 (GAB2), linked to late menarche (beta = 0.140 ¡¾ 0.047, p value = 2.8 ¡¿ 10?3, Bonferroni-corrected p value = 0.049). This result possibly suggests that genetic factors governing AAM in the Korean population would be distinct from those in the Europeans, implying roles of modulating or interacting factors in determining AAM, including environmental factors such as nutritional status.
KEYWORD
GWAS, Age at menarche, Replication, KARE, KoGES, ReproGen consortium
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