Identity-by-descent detection across 487,409 British samples reveals fine scale population structure and ultra-rare variant associations

Nat Commun. 2020 Nov 30;11(1):6130. doi: 10.1038/s41467-020-19588-x.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Genetics, Population*
  • Genome, Human
  • Genome-Wide Association Study
  • Haplotypes
  • Humans
  • Phenotype
  • Quantitative Trait, Heritable
  • United Kingdom
  • White People / genetics*