Whole genome sequencing and imputation in isolated populations identify genetic associations with medically-relevant complex traits.
Nat Commun
; 8: 15606, 2017 05 26.
Article
en En
| MEDLINE
| ID: mdl-28548082
ABSTRACT
Next-generation association studies can be empowered by sequence-based imputation and by studying founder populations. Here we report â¼9.5 million variants from whole-genome sequencing (WGS) of a Cretan-isolated population, and show enrichment of rare and low-frequency variants with predicted functional consequences. We use a WGS-based imputation approach utilizing 10,422 reference haplotypes to perform genome-wide association analyses and observe 17 genome-wide significant, independent signals, including replicating evidence for association at eight novel low-frequency variant signals. Two novel cardiometabolic associations are at lead variants unique to the founder population sequences chr1670790626 (high-density lipoprotein levels beta -1.71 (SE 0.25), P=1.57 × 10-11, effect allele frequency (EAF) 0.006); and rs145556679 (triglycerides levels beta -1.13 (SE 0.17), P=2.53 × 10-11, EAF 0.013). Our findings add empirical support to the contribution of low-frequency variants in complex traits, demonstrate the advantage of including population-specific sequences in imputation panels and exemplify the power gains afforded by population isolates.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Genoma Humano
/
Población Blanca
/
Estudio de Asociación del Genoma Completo
/
Frecuencia de los Genes
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Reino Unido