title: Characterization of Expression Quantitative Trait Loci in Pedigrees from Colombia and Costa Rica Ascertained for Bipolar Disorder.
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.
authors.affiliation: Department of Health Research and Policy, Stanford University, Stanford, California, United States of America.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Peterson
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, United States of America.|Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Service
authors.affiliation: Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Jasinska
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Fuying
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Ivette
authors.initials: I
authors.lastname: Zelaya
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, United States of America.|Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Terri M
authors.initials: TM
authors.lastname: Teshiba
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, United States of America.|Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Bearden
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, United States of America.|Department of Human Genetics, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Rita M
authors.initials: RM
authors.lastname: Cantor
authors.affiliation: Department of Psychiatry, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Victor I
authors.initials: VI
authors.lastname: Reus
authors.affiliation: Cell and Molecular Biology Research Center, Universidad de Costa Rica, San Pedro de Montes de Oca, San José, Costa Rica.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Macaya
authors.affiliation: Grupo de Investigación en Psiquiatría (Research Group in Psychiatry (GIPSI)), Departamento de Psiquiatría, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia; Mood Disorders Program, Hospital San Vicente Fundacion, Medellín, Colombia.
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Jaramillo
authors.affiliation: Faculty of Industrial Engineering and Management, Technion, Haifa, Israel.
authors.forename: Marina
authors.initials: M
authors.lastname: Bogomolov
authors.affiliation: Department of Statistics and Operations Research, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Benjamini
authors.affiliation: Department of Human Genetics, University of California Los Angeles, Los Angeles, California, United States of America.|Department of Computer Science, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Eleazar
authors.initials: E
authors.lastname: Eskin
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, United States of America.|Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, United States of America.|Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Nelson B
authors.initials: NB
authors.lastname: Freimer
authors.affiliation: Department of Biomedical Data Science and Department of Statistics, Stanford University, Stanford, California, United States of America.
authors.forename: Chiara
authors.initials: C
authors.lastname: Sabatti
mesh_terms: D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D003105:Colombia; D003364:Costa Rica; D005260:Female; D015870:Gene Expression; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*