title: Chip-based direct genotyping of coding variants in genome wide association studies: utility, issues and prospects.
abstract: There is considerable debate about the most efficient way to interrogate rare coding variants in association studies. The options include direct genotyping of specific known coding variants in genes or, alternatively, sequencing across the entire exome to capture known as well as novel variants. Each strategy has advantages and disadvantages, but the availability of cost-efficient exome arrays has made the former appealing. Here we consider the utility of a direct genotyping chip, the Illumina HumanExome array (HE), by evaluating its content based on: 1. functionality; and 2. amenability to imputation. We explored these issues by genotyping a large, ethnically diverse cohort on the HumanOmniExpressExome array (HOEE) which combines the HE with content from the GWAS array (HOE). We find that the use of the HE is likely to be a cost-effective way of expanding GWAS, but does have some drawbacks that deserve consideration when planning studies.
authors: Department of Psychiatry, University of California, San Diego; VA Center of Excellence for Stress and Mental Health, VA San Diego. Electronic address: cnievergelt@ucsd.edu.
authors: Caroline M
authors: CM
authors: Nievergelt
authors: Scripps Genomic Medicine, Scripps Health; The Scripps Translational Science Institute, The Scripps Research Institute.
authors: Nathan E
authors: NE
authors: Wineinger
authors: The Scripps Translational Science Institute, The Scripps Research Institute.
authors: Ondrej
authors: O
authors: Libiger
authors: Cypher Genomics, Inc.
authors: Phillip
authors: P
authors: Pham
authors: Human Longevity, Inc.
authors: Guangfa
authors: G
authors: Zhang
authors: Department of Psychiatry, University of California, San Diego; VA Center of Excellence for Stress and Mental Health, VA San Diego.
authors: Dewleen G
authors: DG
authors: Baker
authors: J. Craig Venter Institute. Electronic address: nschork@jcvi.org.
authors: Nicholas J
authors: NJ
authors: Schork
mesh_terms: D000328:Adult; D047369:Chromatin Immunoprecipitation; D059472:Exome; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D055106:Genome-Wide Association Study / Q000379:methods*; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D005819:Genetic Markers
keywords: Coding variants; Expanding GWAS; Genotyping rare SNPs; Illumina HumanExome array