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- Title
Transcriptome-Wide Association Study Identifies Susceptibility Loci and Genes for Age at Natural Menopause.
- Authors
Shi, Jiajun; Wu, Lang; Li, Bingshan; Lu, Yingchang; Guo, Xingyi; Cai, Qiuyin; Long, Jirong; Wen, Wanqing; Zheng, Wei; Shu, Xiao-Ou
- Abstract
Objective: To identify novel susceptibility genes for age at natural menopause (ANM). Methods: Using transcription data generated in tissues from normal hypothalami (n = 73) and ovaries (n = 68) and high-density genotyping data provided by the Genotype-Tissue Expression (GTEx) database, we built 16 164 genetic models to predict gene expression across the transcriptome in these tissues. We used these models and summary statistics data from genome-wide association studies (GWAS) of ANM generated in 69 360 women of European ancestry to identify genes with their predicted expression related to ANM. Results: We found the predicted expression of 34 genes to be significantly associated with ANM at a Bonferroni-corrected threshold of P < 3.09 ×10−6. These include 4 genes located more than 1 Mb away from any previously GWAS-identified ANM-associated variants, 24 genes that reside in known GWAS-identified loci but have not been previously implicated, and 6 genes previously implicated as ANM-associated genes. Conclusion: Results from this transcriptome-wide association study, which integrated Expression quantitative trait loci (eQTL) data with summary statistics of GWAS of ANM, improves our understanding of the genetics and biology of female reproductive aging.
- Subjects
LOCUS (Genetics); GENES; GENE expression; AGE
- Publication
Reproductive Sciences, 2019, Vol 26, Issue 4, p496
- ISSN
1933-7191
- Publication type
Article
- DOI
10.1177/1933719118776788