title: Integrated analyses of gene expression and genetic association studies in a founder population.
abstract: Genome-wide association studies (GWASs) have become a standard tool for dissecting genetic contributions to disease risk. However, these studies typically require extraordinarily large sample sizes to be adequately powered. Strategies that incorporate functional information alongside genetic associations have proved successful in increasing GWAS power. Following this paradigm, we present the results of 20 different genetic association studies for quantitative traits related to complex diseases, conducted in the Hutterites of South Dakota. To boost the power of these association studies, we collected RNA-sequencing data from lymphoblastoid cell lines for 431 Hutterite individuals. We then used Sherlock, a tool that integrates GWAS and expression quantitative trait locus (eQTL) data, to identify weak GWAS signals that are also supported by eQTL data. Using this approach, we found novel associations with quantitative phenotypes related to cardiovascular disease, including carotid intima-media thickness, left atrial volume index, monocyte count and serum YKL-40 levels.
authors.affiliation: Department of Human Genetics and.
authors.forename: Darren A
authors.initials: DA
authors.lastname: Cusanovich
authors.affiliation: Department of Human Genetics and.
authors.forename: Minal
authors.initials: M
authors.lastname: Caliskan
authors.affiliation: Department of Human Genetics and.
authors.forename: Christine
authors.initials: C
authors.lastname: Billstrand
authors.affiliation: Department of Human Genetics and.
authors.forename: Katelyn
authors.initials: K
authors.lastname: Michelini
authors.affiliation: Department of Human Genetics and.
authors.forename: Claudia
authors.initials: C
authors.lastname: Chavarria
authors.affiliation: Department of Human Genetics and.
authors.forename: Sherryl
authors.initials: S
authors.lastname: De Leon
authors.affiliation: Department of Human Genetics and.
authors.forename: Amy
authors.initials: A
authors.lastname: Mitrano
authors.affiliation: Department of Human Genetics and.
authors.forename: Noah
authors.initials: N
authors.lastname: Lewellyn
authors.affiliation: Division of Biology and Medicine, Brown University, Providence, RI 02912, USA and.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Elias
authors.affiliation: Pulmonary and Critical Care, Yale School of Medicine, New Haven, CT 06519, USA.
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Chupp
authors.affiliation: Department of Medicine, Section of Cardiology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Roberto M
authors.initials: RM
authors.lastname: Lang
authors.affiliation: Department of Medicine, Section of Cardiology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Sanjiv J
authors.initials: SJ
authors.lastname: Shah
authors.affiliation: Department of Medicine, Section of Cardiology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Decara
authors.affiliation: Department of Human Genetics and.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Gilad
authors.affiliation: Department of Human Genetics and, c-ober@genetics.uchicago.edu.
authors.forename: Carole
authors.initials: C
authors.lastname: Ober
mesh_terms: D002318:Cardiovascular Diseases / Q000235:genetics* / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D005786:Gene Expression Regulation / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*