Detecting multiple variants associated with disease based on sequencing data of case-parent trios.
J Hum Genet
; 61(10): 851-860, 2016 Oct.
Article
en En
| MEDLINE
| ID: mdl-27278787
ABSTRACT
With the advance of next-generation sequencing technology, the rare variants join the common ones in explaining more proportions of heritability. The coexistence of variants of common with rare, causal with neutral and deleterious with protective is a norm and should be appropriately addressed. Some existing methods suffer from low power when one or more forms of coexistence present, impeding their applications in practice. In this paper, for case-parent trios, pseudocontrols are constructed using the nontransmitted alleles of the parents. The Kullback-Leibler divergence is utilized to measure the difference between the distributions of variants in a genetic region for the affected children and pseudocontrols, and two nonparametric test statistics KLTT and cKLTT are proposed. Extensive simulations show that they are robust to the opposite directions of the causal variants and the amount of neutral variants, and have superiority over the existing methods when both rare and common variants are involved. Furthermore, their efficiency is demonstrated in the application to the data from Framingham Heart Study.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Variación Genética
/
Estudio de Asociación del Genoma Completo
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Hum Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2016
Tipo del documento:
Article
País de afiliación:
China