A fast and efficient approach for gene-based association studies of ordinal phenotypes.
Stat Appl Genet Mol Biol
; 22(1)2023 01 01.
Article
en En
| MEDLINE
| ID: mdl-36724206
ABSTRACT
Many human disease conditions need to be measured by ordinal phenotypes, so analysis of ordinal phenotypes is valuable in genome-wide association studies (GWAS). However, existing association methods for dichotomous or quantitative phenotypes are not appropriate to ordinal phenotypes. Therefore, based on an aggregated Cauchy association test, we propose a fast and efficient association method to test the association between genetic variants and an ordinal phenotype. To enrich association signals of rare variants, we first use the burden method to aggregate rare variants. Then we respectively test the significance of the aggregated rare variants and other common variants. Finally, the combination of transformed variant-level P values is taken as test statistic, that approximately follows Cauchy distribution under the null hypothesis. Extensive simulation studies and analysis of GAW19 show that our proposed method is powerful and computationally fast as a gene-based method. Especially, in the presence of an extremely low proportion of causal variants in a gene, our method has better performance.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Variación Genética
/
Estudio de Asociación del Genoma Completo
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Stat Appl Genet Mol Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA
Año:
2023
Tipo del documento:
Article