title: Mayo Genome Consortia: a genotype-phenotype resource for genome-wide association studies with an application to the analysis of circulating bilirubin levels.
abstract: 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 high-throughput genetic data and electronic medical record (EMR) data for phenotype extraction.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Epidemiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. bielinski.suzette@mayo.edu
authors.forename: Suzette J
authors.initials: SJ
authors.lastname: Bielinski
authors.forename: High Seng
authors.initials: HS
authors.lastname: Chai
authors.forename: Jyotishman
authors.initials: J
authors.lastname: Pathak
authors.forename: Jayant A
authors.initials: JA
authors.lastname: Talwalkar
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Limburg
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Gullerud
authors.forename: Hugues
authors.initials: H
authors.lastname: Sicotte
authors.forename: Eric W
authors.initials: EW
authors.lastname: Klee
authors.forename: Jason L
authors.initials: JL
authors.lastname: Ross
authors.forename: Jean-Pierre A
authors.initials: JP
authors.lastname: Kocher
authors.forename: Iftikhar J
authors.initials: IJ
authors.lastname: Kullo
authors.forename: John A
authors.initials: JA
authors.lastname: Heit
authors.forename: Gloria M
authors.initials: GM
authors.lastname: Petersen
authors.forename: Mariza
authors.initials: M
authors.lastname: de Andrade
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Chute
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001663:Bilirubin / Q000097:blood* / Q000235:genetics; D015331:Cohort Studies; D003362:Cost-Benefit Analysis; D057286:Electronic Health Records; D005260:Female; D055106:Genome-Wide Association Study / Q000191:economics; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D055815:Young Adult; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D014453:Glucuronosyltransferase; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D000099148:UGT1A1 Enzyme; C503999:SLCO1B1 protein, human