Transcriptome-Wide Association Study Identifies Susceptibility Loci and Genes for Age at Natural Menopause

Reproductive Sciences
Jiajun ShiXiao-Ou Shu

Abstract

To identify novel susceptibility genes for age at natural menopause (ANM). 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. 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. 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.

References

Aug 31, 2000·Endocrinology·N HattoriM Ueda
Aug 14, 2008·Menopause : the Journal of the North American Menopause Society·Victor G Vogel
May 19, 2009·Nature Genetics·Lisette StolkAndré G Uitterlinden
Aug 24, 2010·Menopause International·Lynsey Hinds, John Price
Dec 6, 2011·Nature Methods·Olivier DelaneauJean-François Zagury
Apr 28, 2012·Bioinformatics·David S DeLucaGad Getz
Mar 9, 2013·The Journal of Clinical Endocrinology and Metabolism·Changsheng QiuGang Chen
Nov 20, 2013·The Journal of Clinical Endocrinology and Metabolism·Samantha E ParkerElizabeth E Hatch
Dec 18, 2013·Bioinformatics·Andreas KrämerStuart Tugendreich
Feb 25, 2015·Nature Reviews. Genetics·Frank W Albert, Leonid Kruglyak
Aug 11, 2015·Nature Genetics·Eric R GamazonHae Kyung Im
Feb 9, 2016·Nature Genetics·Alexander GusevBogdan Pasaniuc
Aug 2, 2016·The Journal of Clinical Investigation·Joseph R EvansArul M Chinnaiyan
Aug 23, 2016·Nature Genetics·Shane McCarthyUNKNOWN Haplotype Reference Consortium
Sep 9, 2016·International Journal of Molecular Sciences·Stefanie CerkMartin Pichler
Nov 20, 2016·Clinical Genetics·R RossettiL Persani
Feb 28, 2017·American Journal of Human Genetics·Nicholas MancusoBogdan Pasaniuc

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Citations

Mar 2, 2021·Seminars in Reproductive Medicine·Joop S E Laven

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