title: The metabochip, a custom genotyping array for genetic studies of metabolic, cardiovascular, and anthropometric traits.
abstract: Genome-wide association studies have identified hundreds of loci for type 2 diabetes, coronary artery disease and myocardial infarction, as well as for related traits such as body mass index, glucose and insulin levels, lipid levels, and blood pressure. These studies also have pointed to thousands of loci with promising but not yet compelling association evidence. To establish association at additional loci and to characterize the genome-wide significant loci by fine-mapping, we designed the "Metabochip," a custom genotyping array that assays nearly 200,000 SNP markers. Here, we describe the Metabochip and its component SNP sets, evaluate its performance in capturing variation across the allele-frequency spectrum, describe solutions to methodological challenges commonly encountered in its analysis, and evaluate its performance as a platform for genotype imputation. The metabochip achieves dramatic cost efficiencies compared to designing single-trait follow-up reagents, and provides the opportunity to compare results across a range of related traits. The metabochip and similar custom genotyping arrays offer a powerful and cost-effective approach to follow-up large-scale genotyping and sequencing studies and advance our understanding of the genetic basis of complex human diseases and traits.
authors.affiliation: Medical Population Genetics, The Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Voight
authors.forename: Hyun Min
authors.initials: HM
authors.lastname: Kang
authors.forename: Jun
authors.initials: J
authors.lastname: Ding
authors.forename: Cameron D
authors.initials: CD
authors.lastname: Palmer
authors.forename: Carlo
authors.initials: C
authors.lastname: Sidore
authors.forename: Peter S
authors.initials: PS
authors.lastname: Chines
authors.forename: Noël P
authors.initials: NP
authors.lastname: Burtt
authors.forename: Christian
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authors.lastname: Fuchsberger
authors.forename: Yanming
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authors.lastname: Li
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authors.lastname: Erdmann
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
authors.forename: Iris M
authors.initials: IM
authors.lastname: Heid
authors.forename: Anne U
authors.initials: AU
authors.lastname: Jackson
authors.forename: Toby
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authors.lastname: Johnson
authors.forename: Tuomas O
authors.initials: TO
authors.lastname: Kilpeläinen
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Lindgren
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Morris
authors.forename: Inga
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authors.lastname: Prokopenko
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Randall
authors.forename: Richa
authors.initials: R
authors.lastname: Saxena
authors.forename: Nicole
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authors.lastname: Soranzo
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Speliotes
authors.forename: Tanya M
authors.initials: TM
authors.lastname: Teslovich
authors.forename: Eleanor
authors.initials: E
authors.lastname: Wheeler
authors.forename: Jared
authors.initials: J
authors.lastname: Maguire
authors.forename: Melissa
authors.initials: M
authors.lastname: Parkin
authors.forename: Simon
authors.initials: S
authors.lastname: Potter
authors.forename: N William
authors.initials: NW
authors.lastname: Rayner
authors.forename: Neil
authors.initials: N
authors.lastname: Robertson
authors.forename: Kathleen
authors.initials: K
authors.lastname: Stirrups
authors.forename: Wendy
authors.initials: W
authors.lastname: Winckler
authors.forename: Serena
authors.initials: S
authors.lastname: Sanna
authors.forename: Antonella
authors.initials: A
authors.lastname: Mulas
authors.forename: Ramaiah
authors.initials: R
authors.lastname: Nagaraja
authors.forename: Francesco
authors.initials: F
authors.lastname: Cucca
authors.forename: Inês
authors.initials: I
authors.lastname: Barroso
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: Ruth J F
authors.initials: RJ
authors.lastname: Loos
authors.forename: Sekar
authors.initials: S
authors.lastname: Kathiresan
authors.forename: Patricia B
authors.initials: PB
authors.lastname: Munroe
authors.forename: Christopher
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authors.lastname: Newton-Cheh
authors.forename: Arne
authors.initials: A
authors.lastname: Pfeufer
authors.forename: Nilesh J
authors.initials: NJ
authors.lastname: Samani
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
authors.forename: David
authors.initials: D
authors.lastname: Altshuler
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: Gonçalo R
authors.initials: GR
authors.lastname: Abecasis
authors.forename: Michael
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authors.lastname: Boehnke
mesh_terms: D000483:Alleles; D000886:Anthropometry / Q000295:instrumentation* / Q000379:methods; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D005787:Gene Frequency; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D055432:Metabolomics / Q000295:instrumentation* / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis / Q000295:instrumentation* / Q000379:methods; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci