Characterization of Expression Quantitative Trait Loci in Pedigrees from Colombia and Costa Rica Ascertained for Bipolar Disorder

PLoS Genet. 2016 May 13;12(5):e1006046. doi: 10.1371/journal.pgen.1006046. eCollection 2016 May.

Abstract

The observation that variants regulating gene expression (expression quantitative trait loci, eQTL) are at a high frequency among SNPs associated with complex traits has made the genome-wide characterization of gene expression an important tool in genetic mapping studies of such traits. As part of a study to identify genetic loci contributing to bipolar disorder and other quantitative traits in members of 26 pedigrees from Costa Rica and Colombia, we measured gene expression in lymphoblastoid cell lines derived from 786 pedigree members. The study design enabled us to comprehensively reconstruct the genetic regulatory network in these families, provide estimates of heritability, identify eQTL, evaluate missing heritability for the eQTL, and quantify the number of different alleles contributing to any given locus. In the eQTL analysis, we utilize a recently proposed hierarchical multiple testing strategy which controls error rates regarding the discovery of functional variants. Our results elucidate the heritability and regulation of gene expression in this unique Latin American study population and identify a set of regulatory SNPs which may be relevant in future investigations of complex disease in this population. Since our subjects belong to extended families, we are able to compare traditional kinship-based estimates with those from more recent methods that depend only on genotype information.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Bipolar Disorder / genetics*
  • Bipolar Disorder / pathology
  • Chromosome Mapping
  • Colombia
  • Costa Rica
  • Female
  • Gene Expression
  • Gene Regulatory Networks
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Polymorphism, Single Nucleotide / genetics
  • Quantitative Trait Loci / genetics*