The impact of Short Tandem Repeats on grey matter brain imaging derived phenotypes in UK Biobank
Sproviero, W.; Ghose, U.; Winchester, L. M.; Fernandes, M.; Newby, D.; Sproviero, D.; Amin, N.; Smets, B.; He, K. Y.; Khramtsova, E. A.; Patel, P.; Sarver, B. A. J.; Howe, T.; Black, M. H.; van Duijn, C.; Nevado-Holgado, A. J.
Show abstract
We performed a genome-wide association study of 143,067 highly polymorphic short tandem repeats (STRs) with MRI brain grey matter volumes (GMVs) on 10,702 UK Biobank (UKB) participants, including 8,751 in the discovery stage and 1,701 in the replication analysis. STRs repeat lengths were estimated from the UKB whole-genome sequencing data using Expansion Hunter software. A total of 262 STRs reached genome-wide significance in the analyses of the autosomal and sex chromosomes (P = 6.9 x 10-8) in association with MRI -GMVs. Replication in a second batch extraction in the UKB and linkage disequilibrium (LD) analyses confirmed 12 associations of five STRs with hippocampal, intra-calcarine cortex, and cerebellum volumes with no evidence of single nucleotide polymorphisms (SNP) in LD detected in the surrounding DNA regions. Our study highlights the importance of STR variants involved in the genetic architecture of grey matter volumes.
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