A phenome-wide association study of methylated GC-rich repeats identifies a GCC repeat expansion in AFF3 associated with intellectual disability.

ABSTRACT: GC-rich tandem repeat expansions (TREs) are often associated with DNA methylation, gene silencing and folate-sensitive fragile sites, and underlie several congenital and late-onset disorders. Through a combination of DNA-methylation profiling and tandem repeat genotyping, we identified 24 methylated TREs and investigated their effects on human traits using phenome-wide association studies in 168,641 individuals from the UK Biobank, identifying 156 significant TRE-trait associations involving 17 different TREs. Of these, a GCC expansion in the promoter of AFF3 was associated with a 2.4-fold reduced probability of completing secondary education, an effect size comparable to several recurrent pathogenic microdeletions. In a cohort of 6,371 probands with neurodevelopmental problems of suspecte

SUBMITTER: Jadhav B 

PROVIDER: S-EPMC11560504 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature