Unknown

Dataset Information

0

Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia.


ABSTRACT: Genome-wide association studies (GWAS) have identified multiple loci associated with plasma lipid concentrations. Common variants at these loci together explain <10% of variation in each lipid trait. Rare variants with large individual effects may also contribute to the heritability of lipid traits; however, the extent to which rare variants affect lipid phenotypes remains to be determined. Here we show an accumulation of rare variants, or a mutation skew, in GWAS-identified genes in individuals with hypertriglyceridemia (HTG). Through GWAS, we identified common variants in APOA5, GCKR, LPL and APOB associated with HTG. Resequencing of these genes revealed a significant burden of 154 rare missense or nonsense variants in 438 individuals with HTG, compared to 53 variants in 327 controls (P = 6.2 x 10(-8)), corresponding to a carrier frequency of 28.1% of affected individuals and 15.3% of controls (P = 2.6 x 10(-5)). Considering rare variants in these genes incrementally increased the proportion of genetic variation contributing to HTG.

SUBMITTER: Johansen CT 

PROVIDER: S-EPMC3017369 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications


Genome-wide association studies (GWAS) have identified multiple loci associated with plasma lipid concentrations. Common variants at these loci together explain <10% of variation in each lipid trait. Rare variants with large individual effects may also contribute to the heritability of lipid traits; however, the extent to which rare variants affect lipid phenotypes remains to be determined. Here we show an accumulation of rare variants, or a mutation skew, in GWAS-identified genes in individuals  ...[more]

Similar Datasets

| S-EPMC3288444 | biostudies-literature
| S-EPMC3976694 | biostudies-literature
| S-EPMC3953533 | biostudies-literature
| S-EPMC3938989 | biostudies-literature
| S-EPMC7062907 | biostudies-literature
| S-EPMC3620157 | biostudies-literature
| S-EPMC5183500 | biostudies-literature
| S-EPMC3596848 | biostudies-literature
| S-EPMC5505639 | biostudies-literature
| S-EPMC4309561 | biostudies-literature