Accuracy of haplotype estimation and whole genome imputation affects complex trait analyses in complex biobanks.
Commun Biol
; 6(1): 101, 2023 01 26.
Article
en En
| MEDLINE
| ID: mdl-36697501
ABSTRACT
Sample recruitment for research consortia, biobanks, and personal genomics companies span years, necessitating genotyping in batches, using different technologies. As marker content on genotyping arrays varies, integrating such datasets is non-trivial and its impact on haplotype estimation (phasing) and whole genome imputation, necessary steps for complex trait analysis, remains under-evaluated. Using the iPSYCH dataset, comprising 130,438 individuals, genotyped in two stages, on different arrays, we evaluated phasing and imputation performance across multiple phasing methods and data integration protocols. While phasing accuracy varied by choice of method and data integration protocol, imputation accuracy varied mostly between data integration protocols. We demonstrate an attenuation in imputation accuracy within samples of non-European origin, highlighting challenges to studying complex traits in diverse populations. Finally, imputation errors can bias association tests, reduce predictive utility of polygenic scores. Carefully optimized data integration strategies enhance accuracy and replicability of complex trait analyses in complex biobanks.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Bancos de Muestras Biológicas
/
Herencia Multifactorial
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Commun Biol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Dinamarca