AI Article Synopsis
- This study investigates multi-allelic variations of tandem repeats (TRs) and their impact on human traits, using data from over 168,000 individuals in the UK Biobank.
- Researchers identified 47 TRs that are linked to 73 different traits, with a successful replication rate of 74% in another cohort.
- The findings suggest that common variations in TR length contribute to human traits and gene expression, providing insights into the genetic factors behind the "missing heritability" in genetics.
Article Abstract
Most genetic association studies focus on binary variants. To identify the effects of multi-allelic variation of tandem repeats (TRs) on human traits, we perform direct TR genotyping and phenome-wide association studies in 168,554 individuals from the UK Biobank, identifying 47 TRs showing fine-mapped associations with 73 traits. We replicate 23 of 31 (74%) of these associations in the All of Us cohort. While this set includes several known repeat expansion disorders, novel associations we found are attributable to common polymorphic variation in TR length rather than rare expansions and include e.g. a coding polyhistidine motif in HRCT1 influencing risk of hypertension and a poly(CGC) in the 5'UTR of GNB2 influencing heart rate. Fine-mapped TRs are strongly enriched for associations with local gene expression and DNA methylation. Our study highlights the contribution of multi-allelic TRs to the "missing heritability" of the human genome.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614882 | PMC |
| http://dx.doi.org/10.1038/s41467-024-54678-0 | DOI Listing |
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