NG00196- Genotyping short tandem repeats using the ADSP R4 cohort

A two-step pipeline was used to first identify expanded short tandem repeats (STRs) in ADSP samples using ExpansionHunter Denovo and then genotype the identified STRs, along with additional polymorphic STRs identified from population surveys, using ExpansionHunter.

ADSP R4 genomes were profiled using ExpansionHunter Denovo to identify putative STR expansions. Single-sample profiles were merged into multi-sample profiles, and raw read counts were extracted. Since ExpansionHunter Denovo outputs a candidate region and expanded STR motif, a custom pipeline was created to convert these candidate regions/motifs into an ExpansionHunter catalog comprising the best estimate of STR start and end coordinates. In this step, STR regions supported by at least two raw in-repeat reads (IRRs) identified by ExpansionHunter Denovo were retained. These regions were supplemented with additional STRs that were either highly polymorphic or showed evidence of expansion from prior profiling of 22,579 individuals of diverse ancestry, as previously described (PMID: 39627187).

The resulting catalog comprised 165,208 STR loci with motif sizes ranging from 2 to 20 bp. This ExpansionHunter catalog was subsequently used to genotype STRs in the Illumina whole-genome sequencing data from the ADSP R4 data release.

One sample was dropped due to a sex mismatch, five samples were dropped due to being labeled with the incorrect sex, and one sample was dropped due to consent. Phenotypes are not provided directly within this dataset but are available through request of the ADSP Umbrella dataset (ng00067).