Examination of genetic variants influencing lipid traits in pediatric populations.
J Pediatr Genet
; 1(2): 85-98, 2012 Jun.
Article
em En
| MEDLINE
| ID: mdl-27625808
ABSTRACT
Previous large-scale genome-wide association studies in adult populations have implicated â½100 loci in determining high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, or triglyceride levels. However, whether these loci also contribute to variations of lipid traits in pediatric populations remain unknown. Here we assayed a population of Philadelphia children by high-density single nucleotide polymorphism arrays, and performed association analysis on lipid traits ascertained from lipid measurements stored in electronic medical records. We examined previously reported lipid trait associations, and found that most of them show identical direction of association in our pediatric cohorts, including genome-wide significant association on cholesteryl ester transfer protein with HDL-C levels (rs3764261, P = 2.1 × 10(-8)) and other significant associations on oxysterol-binding protein-like protein 7, low-density lipoprotein receptor-related protein 4 and low-density lipoprotein receptor-related protein 1. Additionally, we identified suggestive association on low-density lipoprotein receptor-related protein 1B with HDL-C levels (rs17736712, P = 2.1 × 10(-7)), but this signal is not supported by previous meta-analysis on adult cohorts. Finally, we examined rare copy number variants and identified deletions encompassing tetratricopeptide repeat domain 39B in two children with extreme lipid measures. Our results highlight the commonalities and differences of genetic components in determining lipid traits in pediatric versus adult populations. Furthermore, our study demonstrates the unique utility of automated information retrieval from electronic medical records in facilitating the identification of genotype-phenotype associations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
J Pediatr Genet
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos