DNA-methylation (DNAm) can be widely linked to aging using age-associated CpG sites (CpGs). Moreover, studies have shown that DNAm profiles can serve as preditors of all-cause mortality. Epigenome-wide association studies (EWAS) have been frequently performed to look for epigenetic markers of aging and mortality. Earlier it has not been possible to analyze the X-chromosome because of limited sample size because of the fact that females (two) and males (one) have distinct patterns of methylation on the X-chromosome which prevents joint analysis on the two sexes. Now, using the Lothian Birth Cohort datasets (1921, 1936) combined, we here propose an exploratory study for sex-specific X-linked DNAm analysis using the Cox proportional hazard model with time-dependent covariates, with and without L1/L2 penalization, for males (N=668) and females (N=757) separately. Our results show two significant CpGs highly associated with mortality for males with FDR<0.05 (cg02698668, coef -0.74; cg14894216, coef -0.84 and candidate sites for further investigation for the females. Marker cg14894216 is located in the promotor region of CATSPER1, a gene that plays a primary role in the regulation of sperm motility, with the latter having been confirmed to affect male mortality by epidemiological studies. We conclude that X-chromosome could play an important role in the sex-specific epigenetic regulation of all-cause mortality in the elderly population.
|Status||Udgivet - jun. 2017|
|Begivenhed||13th Annual Meeting of the International Symposium on Integrative Bioinformatics - University of Southern Denmark, Campusvej 55 5230 Odense, Odense, Danmark|
Varighed: 22. jun. 2017 → 24. jun. 2017
Konferencens nummer: 13
|Konference||13th Annual Meeting of the International Symposium on Integrative Bioinformatics|
|Lokation||University of Southern Denmark, Campusvej 55 5230 Odense|
|Periode||22/06/2017 → 24/06/2017|