A Genome-Wide Association Study on Cataract and HDL in the Personalized Medicine Research Project Cohort

The primary goals of this project are to develop and validate electronic phenotyping algorithms, to accurately identify cases and controls while maintaining a positive predictive value (PPV) of >95%, and to conduct a genome wide association study that advances understanding of two specific yet interrelated disease states, while simultaneously engaging the community in these research efforts. Lipid abnormalities and cataracts are both diseases of public health significance, they share common risk factors, and they are both complex diseases which likely have many genes contributing to disease development. Whole genome association studies with these two outcomes and environmental risk factors could yield novel data about the etiology of the two separate outcomes as well as their interaction.

PhenX is a project designed to prioritize Phenotypes and eXposure measures for Genome-wide Association Studies (GWAS). The PhenX Toolkit is a valuable resource for researchers who are planning or expanding a study and would like to incorporate well established measures that have been recommended by experts in the field. We are currently interested in gene-environment interactions for "age related cataract".

• Study Weblinks:
  • Personalized Medicine Research Project
• Study Design:
  • Case-Control
• Study Type:
  • Case-Control
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 3989
• Subject Sample Telemetry Report (SSTR)

• BioProject
• PubMed
• BioSample
• MeSH
• PMC

Cataract - (Please see additional document Marshfield-CataractDefinition)
Low HDL - (Please see additional document Marshfield-LowHDLDefinition)

Cataract and HDL Time Line

• September 2002 - Personalized Medicine Research Project (PMRP) launches recruitment
• November 2007 - IRB officially approves the 1st GWAS study for Personalized Medicine to be included in a data-repository (dbGaP)
• December 2007 - Cut-off date for Cataract and Low HDL cohort enrollment
• January 2008 - Began phenotyping process
• January 2009 - Selected samples to be genotyped
• February 2009 - Samples shipped and received at CIDR
• August 2010 - Samples shipped to CIDR for Resistant hypertension
• October 2010 - Samples shipped to CIDR for Glaucoma
• October 2011 - Collected additional phenotypic data from the PhenX Toolkit

Funding for data collection with PhenX variables has been provided by the NHGRI PhenX RISING program.

• Primary Phenotype: Cataract
• Cholesterol, HDL
• Lipoproteins, HDL
• Glaucoma
• Hypertension

• Principal Investigator
  • Catherine A. McCarty, PhD, MPH. Marshfield Clinic Research Foundation, Marshfield, WI; Essentia Institute of Rural Health, Duluth, MN, USA.
• Principal Investigator-Site
  • Murray Brilliant, PhD. Marshfield Clinic Research Foundation, Marshfield, WI, USA.
  • Marylyn Ritchie, PhD. The Pennsylvania State University, University Park, PA , USA.
• Funding Source
  • 1U01HG004608-01. National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • 3U01HG006389-01S1. National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
• Genotyping Center
  • Johns Hopkins University Center for Inherited Disease Research (CIDR), Baltimore, MD, USA.
• Funding Source for Genotyping
  • U01HG004438-01. National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.