| Title: | Identity-by-descent detection across 487,409 British samples reveals fine scale population structure and ultra-rare variant associations |
| Journal: | Nature Communications |
| Published: | 30 Nov 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33257650/ |
| DOI: | https://doi.org/10.1038/s41467-020-19588-x |
| URL: | https://www.nature.com/articles/s41467-020-19588-x.pdf |
| Citations: | 82 (46 in last 2 years) as of 8 Aug 2024 |
Publication 3624
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Abstract
Detection of Identical-By-Descent (IBD) segments provides a fundamental measure of genetic relatedness and plays a key role in a wide range of analyses. We develop FastSMC, an IBD detection algorithm that combines a fast heuristic search with accurate coalescent-based likelihood calculations. FastSMC enables biobank-scale detection and dating of IBD segments within several thousands of years in the past. We apply FastSMC to 487,409 UK Biobank samples and detect ~214 billion IBD segments transmitted by shared ancestors within the past 1500 years, obtaining a fine-grained picture of genetic relatedness in the UK. Sharing of common ancestors strongly correlates with geographic distance, enabling the use of genomic data to localize a sample's birth coordinates with a median error of 45 km. We seek evidence of recent positive selection by identifying loci with unusually strong shared ancestry and detect 12 genome-wide significant signals. We devise an IBD-based test for association between phenotype and ultra-rare loss-of-function variation, identifying 29 association signals in 7 blood-related traits.</p>
7 Authors
- Juba Nait Saada
- Georgios Kalantzis
- Derek Shyr
- Fergus Cooper
- Martin Robinson
- Alexander Gusev
- Pier Francesco Palamara
1 Application
| Application ID | Title |
|---|---|
| 43206 | Statistical methods for large-scale genomic analysis |
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