RXRG
Retinoic acid receptor RXR-gamma (Nuclear receptor subfamily 2 group B member 3) (Retinoid X receptor gamma) [NR2B3]
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Reproductive aging phenotypes, including age at menarche (AM) and age at natural menopause (ANM), are well-established risk factors for breast cancer. In recent years, many genetic variants have been identified in association with AM and ANM in genome-wide association studies among European populations. Using data from the Women's Circle of Health Study (WCHS) of 1,307 European-American (EA) and 1,365 African-American (AA) breast cancer cases and controls, we aimed to replicate 53 earlier GWAS variants for AM and ANM in AA and EA groups and to perform analyses on total and net reproductive lifespan (TRLS; NRLS). Breast cancer risk was also examined in relation to a polygenic risk score (PRS) for each of the reproductive aging phenotypes. We replicated a number of variants in EA women, including rs7759938 in LIN28B for AM and rs16991615 in MCM8 for ANM; whereas in the AA group, only one SNP (rs2947411 in TMEM18) for AM was directionally consistent and nominally significant. In analysis of TRLS and NRLS, several SNPs were significant, including rs466639 in RXRG that was associated with both phenotypes in both AA and EA groups. None of the PRS was associated with breast cancer risk. Given the paucity of data available among AA populations, our study contributes to the literature of genetics of reproductive aging in AA women and highlights the importance of cross population replication of GWAS variants.
MeSH Terms
- Adult
- African Americans
- Aged
- Aging
- Breast Neoplasms
- European Continental Ancestry Group
- Female
- Genetic Predisposition to Disease
- Genetic Variation
- Humans
- Menarche
- Menopause
- Middle Aged
- Polymorphism, Single Nucleotide
- Reproduction
- Risk Factors
- Young Adult
Age at menarche (AAM) is a complex trait involving both genetic and environmental factors. To identify the genetic factors associated with AAM, we conducted a large-scale meta-analysis of genome-wide association studies using more than 15,000 Japanese female samples. Here, we identified an association between SNP (single nucleotide polymorphism) rs364663 at the LIN28B locus and AAM, with a P-value of 5.49×10(-7) and an effect size of 0.089 (year). We also evaluated 33 SNPs that were previously reported to be associated with AAM in women of European ancestry. Among them, two SNPs rs4452860 and rs7028916 in TMEM38B indicated significant association with AAM in the same directions as reported in previous studies (P = 0.0013 with an effect size of 0.051) even after Bonferroni correction for the 33 SNPs. In addition, six loci in or near CCDC85A, LOC100421670, CA10, ZNF483, ARNTL, and RXRG exhibited suggestive association with AAM (P<0.05). Our findings elucidated the impact of genetic variations on AAM in the Japanese population.
MeSH Terms
- Age Factors
- Aging
- Asian Continental Ancestry Group
- European Continental Ancestry Group
- Female
- Genome-Wide Association Study
- Humans
- Japan
- Menarche
- Meta-Analysis as Topic
- Polymorphism, Single Nucleotide