TY - JOUR
T1 - Mayo genome consortia
T2 - A genotype-phenotype resource for genome-wide association studies with an application to the analysis of circulating bilirubin levels
AU - Bielinski, Suzette J.
AU - Chai, High Seng
AU - Pathak, Jyotishman
AU - Talwalkar, Jayant A.
AU - Limburg, Paul J.
AU - Gullerud, Rachel E.
AU - Sicotte, Hugues
AU - Klee, Eric W.
AU - Ross, Jason L.
AU - Kocher, Jean Pierre A.
AU - Kullo, Iftikhar J.
AU - Heit, John A.
AU - Petersen, Gloria M.
AU - De Andrade, Mariza
AU - Chute, Christopher G.
N1 - Funding Information:
Funding for this research was provided by the Electronic Medical Records and Genomics (eMERGE) Network of the National Human Genome Research Institute (HG05499), Mayo Clinic Genome-wide Association Study of Venous Thromboembolism (HG04735) from the National Human Genome Research Institute (NHGRI; Gene Environment Association Studies [GENEVA] consortium), Mayo Clinic Specialized Programs of Research Excellence (SPORE) in Pancreatic Cancer (P50CA102701) from the National Cancer Institute, and Mayo Clinic Cancer Center (Genetic Epidemiology and Risk Assessment [GERA] Program). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr Limburg served as a consultant for Genomic Health, Inc from August 12, 2008, through April 19, 2010. Mayo Clinic has licensed Dr Limburg's intellectual property to Exact Sciences, and he and Mayo Clinic have contractual rights to receive royalties through this agreement.
PY - 2011/7
Y1 - 2011/7
N2 - OBJECTIVE: To create a cohort for cost-effective genetic research, the Mayo Genome Consortia (MayoGC) has been assembled with participants from research studies across Mayo Clinic with highthroughput genetic data and electronic medical record (EMR) data for phenotype extraction. PARTICIPANTS AND METHODS: Eligible participants include those who gave general research consent in the contributing studies to share high-throughput genotyping data with other investigators. Herein, we describe the design of the MayoGC, including the current participating cohorts, expansion efforts, data processing, and study management and organization. A genome-wide association study to identify genetic variants associated with total bilirubin levels was conducted to test the genetic research capability of the MayoGC. RESULTS: Genome-wide significant results were observed on 2q37 (top single nucleotide polymorphism, rs4148325; P=5.0 × 10-62) and 12p12 (top single nucleotide polymorphism, rs4363657; P=5.1 × 10-8) corresponding to a gene cluster of uridine 5′-diphospho-glucuronosyltransferases (the UGT1A cluster) and solute carrier organic anion transporter family, member 1B1 (SLCO1B1), respectively. CONCLUSION: Genome-wide association studies have identified genetic variants associated with numerous phenotypes but have been historically limited by inadequate sample size due to costly genotyping and phenotyping. Large consortia with harmonized genotype data have been assembled to attain sufficient statistical power, but phenotyping remains a rate-limiting factor in gene discovery research efforts. The EMR consists of an abundance of phenotype data that can be extracted in a relatively quick and systematic manner. The MayoGC provides a model of a unique collaborative effort in the environment of a common EMR for the investigation of genetic determinants of diseases.
AB - OBJECTIVE: To create a cohort for cost-effective genetic research, the Mayo Genome Consortia (MayoGC) has been assembled with participants from research studies across Mayo Clinic with highthroughput genetic data and electronic medical record (EMR) data for phenotype extraction. PARTICIPANTS AND METHODS: Eligible participants include those who gave general research consent in the contributing studies to share high-throughput genotyping data with other investigators. Herein, we describe the design of the MayoGC, including the current participating cohorts, expansion efforts, data processing, and study management and organization. A genome-wide association study to identify genetic variants associated with total bilirubin levels was conducted to test the genetic research capability of the MayoGC. RESULTS: Genome-wide significant results were observed on 2q37 (top single nucleotide polymorphism, rs4148325; P=5.0 × 10-62) and 12p12 (top single nucleotide polymorphism, rs4363657; P=5.1 × 10-8) corresponding to a gene cluster of uridine 5′-diphospho-glucuronosyltransferases (the UGT1A cluster) and solute carrier organic anion transporter family, member 1B1 (SLCO1B1), respectively. CONCLUSION: Genome-wide association studies have identified genetic variants associated with numerous phenotypes but have been historically limited by inadequate sample size due to costly genotyping and phenotyping. Large consortia with harmonized genotype data have been assembled to attain sufficient statistical power, but phenotyping remains a rate-limiting factor in gene discovery research efforts. The EMR consists of an abundance of phenotype data that can be extracted in a relatively quick and systematic manner. The MayoGC provides a model of a unique collaborative effort in the environment of a common EMR for the investigation of genetic determinants of diseases.
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U2 - 10.4065/mcp.2011.0178
DO - 10.4065/mcp.2011.0178
M3 - Article
C2 - 21646302
AN - SCOPUS:79959693383
SN - 0025-6196
VL - 86
SP - 606
EP - 614
JO - Mayo Clinic proceedings
JF - Mayo Clinic proceedings
IS - 7
ER -