Identity-by-descent detection across 487,409 British samples reveals fine scale population structure and ultra-rare variant associations.
Nat Commun
; 11(1): 6130, 2020 11 30.
Article
em En
| MEDLINE
| ID: mdl-33257650
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
População Branca
/
Genética Populacional
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
País/Região como assunto:
Europa
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2020
Tipo de documento:
Article