title: Electronic medical records and genomics (eMERGE) network exploration in cataract: several new potential susceptibility loci.
abstract: OBJECTIVE
  Cataract is the leading cause of blindness in the world, and in the United States accounts for approximately 60% of Medicare costs related to vision. The purpose of this study was to identify genetic markers for age-related cataract through a genome-wide association study (GWAS).
  
  
  METHODS
  In the electronic medical records and genomics (eMERGE) network, we ran an electronic phenotyping algorithm on individuals in each of five sites with electronic medical records linked to DNA biobanks. We performed a GWAS using 530,101 SNPs from the Illumina 660W-Quad in a total of 7,397 individuals (5,503 cases and 1,894 controls). We also performed an age-at-diagnosis case-only analysis.
  
  
  RESULTS
  We identified several statistically significant associations with age-related cataract (45 SNPs) as well as age at diagnosis (44 SNPs). The 45 SNPs associated with cataract at p<1×10(-5) are in several interesting genes, including ALDOB, MAP3K1, and MEF2C. All have potential biologic relationships with cataracts.
  
  
  CONCLUSIONS
  This is the first genome-wide association study of age-related cataract, and several regions of interest have been identified. The eMERGE network has pioneered the exploration of genomic associations in biobanks linked to electronic health records, and this study is another example of the utility of such resources. Explorations of age-related cataract including validation and replication of the association results identified herein are needed in future studies.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA.
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA.
authors.forename: Shefali S
authors.initials: SS
authors.lastname: Verma
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA.
authors.forename: Molly A
authors.initials: MA
authors.lastname: Hall
authors.affiliation: Center for Human Genetics Research, Vanderbilt University, Nashville, TN.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Goodloe
authors.affiliation: Biomedical Informatics Research Center, Biostatistics, Marshfield Clinic Research Foundation, Marshfield, WI.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Berg
authors.affiliation: Group Health Research Institute, Seattle, WA.
authors.forename: Dave S
authors.initials: DS
authors.lastname: Carrell
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Carlson
authors.affiliation: Ophthalmology, Marshfield Clinic Research Foundation, Marshfield, WI.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Division of Medical Genetics, University of Washington, Seattle, WA ; Department of Biostatistics, University of Washington, Seattle, WA.
authors.forename: David R
authors.initials: DR
authors.lastname: Crosslin
authors.affiliation: Departments of Biomedical Informatics, Vanderbilt University, Nashville, TN ; Department of Medicine, Vanderbilt University, Nashville, TN.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Denny
authors.affiliation: Division of Medical Genetics, University of Washington, Seattle, WA ; Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA.
authors.forename: Gail
authors.initials: G
authors.lastname: Jarvik
authors.affiliation: Office of Population Genomics, National Human Genome Research Institute, Bethesda, MD.
authors.forename: Rongling
authors.initials: R
authors.lastname: Li
authors.affiliation: Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, WI.
authors.forename: James G
authors.initials: JG
authors.lastname: Linneman
authors.affiliation: Department of Biomedical Informatics, Mayo Clinic College of Medicine, Rochester, MN.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Pathak
authors.affiliation: Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, WI.
authors.forename: Peggy
authors.initials: P
authors.lastname: Peissig
authors.affiliation: Division of Health and Biomedical Informatics, Department of Preventive Medicine, Northwestern University, Chicago, IL.
authors.forename: Luke V
authors.initials: LV
authors.lastname: Rasmussen
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN.
authors.forename: Andrea H
authors.initials: AH
authors.lastname: Ramirez
authors.affiliation: Departments of Biomedical Informatics, Vanderbilt University, Nashville, TN.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wang
authors.affiliation: Departments of Biomedical Informatics, Vanderbilt University, Nashville, TN ; IMAGENETICS at Sanford Medical Center, Fargo, ND and Department of Internal Medicine, University of North Dakota, Fargo, ND.
authors.forename: Russell A
authors.initials: RA
authors.lastname: Wilke
authors.affiliation: Division of Genetics and Genomics, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Wolf
authors.affiliation: Center for Human Genetics Research, Vanderbilt University, Nashville, TN.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Torstenson
authors.affiliation: Public Health Sciences, University of Virginia, Charlottesville, VA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Turner
authors.affiliation: Essentia Institute of Rural Health, Duluth, MN.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: McCarty
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D002386:Cataract / Q000235:genetics* / Q000473:pathology; D030561:Databases, Nucleic Acid; D057286:Electronic Health Records / Q000706:statistics & numerical data*; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D017048:Health Care Costs; D006801:Humans; D048728:MAP Kinase Kinase Kinase 1 / Q000235:genetics*; D064326:MEF2 Transcription Factors / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D014481:United States
chemical_list: D005819:Genetic Markers; D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human; D005634:Fructose-Bisphosphate Aldolase