The metabochip, a custom genotyping array for genetic studies of metabolic, cardiovascular, and anthropometric traits

TY - JOUR

T1 - The metabochip, a custom genotyping array for genetic studies of metabolic, cardiovascular, and anthropometric traits

AU - Voight, Benjamin F

AU - Kang, Hyun Min

AU - Ding, Jun

AU - Palmer, Cameron D

AU - Sidore, Carlo

AU - Chines, Peter S

AU - Burtt, Noël P

AU - Fuchsberger, Christian

AU - Li, Yanming

AU - Erdmann, Jeanette

AU - Frayling, Timothy M

AU - Heid, Iris M

AU - Jackson, Anne U

AU - Johnson, Toby

AU - Oskari Kilpeläinen, Tuomas

AU - Lindgren, Cecilia M

AU - Morris, Andrew P

AU - Prokopenko, Inga

AU - Randall, Joshua C

AU - Saxena, Richa

AU - Soranzo, Nicole

AU - Speliotes, Elizabeth K

AU - Teslovich, Tanya M

AU - Wheeler, Eleanor

AU - Maguire, Jared

AU - Parkin, Melissa

AU - Potter, Simon

AU - Rayner, N William

AU - Robertson, Neil

AU - Stirrups, Kathleen

AU - Winckler, Wendy

AU - Sanna, Serena

AU - Mulas, Antonella

AU - Nagaraja, Ramaiah

AU - Cucca, Francesco

AU - Barroso, Inês

AU - Deloukas, Panos

AU - Loos, Ruth J F

AU - Kathiresan, Sekar

AU - Munroe, Patricia B

AU - Newton-Cheh, Christopher

AU - Pfeufer, Arne

AU - Samani, Nilesh J

AU - Schunkert, Heribert

AU - Hirschhorn, Joel N

AU - Altshuler, David

AU - McCarthy, Mark I

AU - Abecasis, Gonçalo R

AU - Boehnke, Michael

PY - 2012/8

Y1 - 2012/8

N2 - 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.

AB - 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.

KW - Alleles

KW - Anthropometry

KW - Cardiovascular Diseases

KW - Diabetes Mellitus, Type 2

KW - Gene Frequency

KW - Genome, Human

KW - Genome-Wide Association Study

KW - Genotype

KW - Genotyping Techniques

KW - Humans

KW - Metabolomics

KW - Oligonucleotide Array Sequence Analysis

KW - Phenotype

KW - Polymorphism, Single Nucleotide

KW - Quantitative Trait Loci

U2 - 10.1371/journal.pgen.1002793

DO - 10.1371/journal.pgen.1002793

M3 - Journal article

C2 - 22876189

SN - 1553-7390

VL - 8

SP - e1002793

JO - P L o S Genetics

JF - P L o S Genetics

IS - 8

ER -