Improved imputation accuracy in Hispanic/Latino populations with larger and more diverse reference panels: applications in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
Hum Mol Genet
; 25(15): 3245-3254, 2016 08 01.
Article
en En
| MEDLINE
| ID: mdl-27346520
ABSTRACT
Imputation is commonly used in genome-wide association studies to expand the set of genetic variants available for analysis. Larger and more diverse reference panels, such as the final Phase 3 of the 1000 Genomes Project, hold promise for improving imputation accuracy in genetically diverse populations such as Hispanics/Latinos in the USA. Here, we sought to empirically evaluate imputation accuracy when imputing to a 1000 Genomes Phase 3 versus a Phase 1 reference, using participants from the Hispanic Community Health Study/Study of Latinos. Our assessments included calculating the correlation between imputed and observed allelic dosage in a subset of samples genotyped on a supplemental array. We observed that the Phase 3 reference yielded higher accuracy at rare variants, but that the two reference panels were comparable at common variants. At a sample level, the Phase 3 reference improved imputation accuracy in Hispanic/Latino samples from the Caribbean more than for Mainland samples, which we attribute primarily to the additional reference panel samples available in Phase 3. We conclude that a 1000 Genomes Project Phase 3 reference panel can yield improved imputation accuracy compared with Phase 1, particularly for rare variants and for samples of certain genetic ancestry compositions. Our findings can inform imputation design for other genome-wide association studies of participants with diverse ancestries, especially as larger and more diverse reference panels continue to become available.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Hispánicos o Latinos
/
Proyecto Genoma Humano
/
Estudio de Asociación del Genoma Completo
Límite:
Female
/
Humans
/
Male
País/Región como asunto:
America do norte
Idioma:
En
Revista:
Hum Mol Genet
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos