Very low-depth sequencing in a founder population identifies a cardioprotective APOC3 signal missed by genome-wide imputation.
Hum Mol Genet
; 25(11): 2360-2365, 2016 06 01.
Article
em En
| MEDLINE
| ID: mdl-27146844
ABSTRACT
Cohort-wide very low-depth whole-genome sequencing (WGS) can comprehensively capture low-frequency sequence variation for the cost of a dense genome-wide genotyping array. Here, we analyse 1x sequence data across the APOC3 gene in a founder population from the island of Crete in Greece (n = 1239) and find significant evidence for association with blood triglyceride levels with the previously reported R19X cardioprotective null mutation (ß = -1.09,σ = 0.163, P = 8.2 × 10-11) and a second loss of function mutation, rs138326449 (ß = -1.17,σ = 0.188, P = 1.14 × 10-9). The signal cannot be recapitulated by imputing genome-wide genotype data on a large reference panel of 5122 individuals including 249 with 4x WGS data from the same population. Gene-level meta-analysis with other studies reporting burden signals at APOC3 provides robust evidence for a replicable cardioprotective rare variant aggregation (P = 3.2 × 10-31, n = 13 480).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Triglicerídeos
/
Doenças Cardiovasculares
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Apolipoproteína C-III
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Sequenciamento de Nucleotídeos em Larga Escala
Tipo de estudo:
Systematic_reviews
Limite:
Female
/
Humans
/
Male
País/Região como assunto:
Europa
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article