Introduction. The eMERGE (electronic MEdical Records and GEnomics) Network is an NHGRI-supported consortium of five institutions to explore the utility of DNA repositories coupled to Electronic Medical Record (EMR) systems for advancing discovery in genome science. eMERGE also includes a special emphasis on the ethical, legal and social issues related to these endeavors. Organization. The five sites are supported by an Administrative Coordinating Center. Setting of network goals is initiated by working groups: (1) Genomics, (2) Informatics, and (3) Consent & Community Consultation, which also includes active participation by investigators outside the eMERGE funded sites, and (4) Return of Results Oversight Committee. The Steering Committee, comprised of site PIs and representatives and NHGRI staff, meet three times per year, once per year with the External Scientific Panel. Current progress. The primary site-specific phenotypes for which samples have undergone genome-wide association study (GWAS) genotyping are cataract and HDL, dementia, electrocardiographic QRS duration, peripheral arterial disease, and type 2 diabetes. A GWAS is also being undertaken for resistant hypertension in 2,000 additional samples identified across the network sites, to be added to data available for samples already genotyped. Funded by ARRA supplements, secondary phenotypes have been added at all sites to leverage the genotyping data, and hypothyroidism is being analyzed as a cross-network phenotype. Results are being posted in dbGaP. Other key eMERGE activities include evaluation of the issues associated with cross-site deployment of common algorithms to identify cases and controls in EMRs, data privacy of genomic and clinically-derived data, developing approaches for large-scale meta-analysis of GWAS data across five sites, and a community consultation and consent initiative at each site. Future activities. Plans are underway to expand the network in diversity of populations and incorporation of GWAS findings into clinical care. Summary. By combining advanced clinical informatics, genome science, and community consultation, eMERGE represents a first step in the development of data-driven approaches to incorporate genomic information into routine healthcare delivery.
Bibliographical noteFunding Information:
The specific aim of the Mayo supplementary proposal is to identify genomic loci influencing red blood cell (RBC) indices using a GWAS approach in cohorts of the eMERGE network. The RBC indices include RBC count, hemoglobin level, mean corpuscular volume, mean corpuscular hemoglobin, RBC distribution width and erythrocyte sedimentation rate. The findings from the proposed analyses will help to characterize molecular mechanisms underlying inter-individual variability in RBC indices, provide novel insights into anemia and related hematologic diseases, and could eventually contribute to the development of new therapeutic approaches for such diseases. Community Consultation Since genomic data cannot easily or with certainty be fully de-identified or anonymized, an important aim of the Mayo eMERGE project is to engage extensively with research participants and the community regarding best practices to weigh the future benefits of genomic research to patients, families, and the society against the potential risks. The investigators will develop and refine consenting procedures in collaboration with Mayo’s IRB on the basis of these findings, through an “Ethics Incubator” developed as part of Mayo’s Clinical and Translational Science Award (CTSA). A combination of in-depth patient interviews, consenting “experiments”, and community engagement using Deliberative Democracy methods are being employed. Group Health Cooperative, University of Washington and the Fred Hutchinson Cancer Research Center Biobank description The Group Health (GH) biobank for eMERGE is based within an established and growing cohort of 3,793 patients recruited within GH and actively followed for Alzheimer’s Disease (AD) and dementia. Two sub-samples from GH form the specific population analyzed in this project. The Alzheimer’s Disease Patient Registry (ADPR)  was established in 1986. A related study, Genetic Differences, allowed collection of DNA for persons in the ADPR. The ADPR was complemented in 1994-1996 and ultimately succeeded by the prospective Adult Changes in Thought (ACT) study . Both ADPR and ACT were initiated - and continue in their 23rd year - with funding from a U01 from the National Institute on Aging. ADPR enrolled 695 dementia cases from GH. ACT enrolled 2,581 dementia-free individuals in 1994-1996, with 811 additional dementia-free individuals from 2000-2002, and has since 2005 been enrolling dementia-free subjects continuously with identical methods to keep at least 2000 person-years under observation at all times. DNA is available on 95% of the cohort. The ACT subsample is well-characterized, with research assessments every 2 years of risk factors, cognition, blood pressure, physical performance, over-the-counter medication use, and other research-quality study data on both phenotypes and environmental exposures. The ACT sub-sample is stable; for the original cohort, median enrollment in GH was 19 years prior to joining the ACT study, and 85% of the cohort has ≥10 years of GH enrollment. This is a useful cohort for population-based genome-wide GWA studies and offers the somewhat unique characteristic of very long-term longitudinal data. The cohort also has noteworthy value as controls for subsequent GWA analyses of other phenotypes, as it is well-characterized, and many participants have lived to advanced old age under continuous observation. eMERGE project aims Phenotypes Group Health’s primary phenotype of interest is Alzheimer’s Disease (AD) using dementia cases and controls within the GH biorepository, based on gold-standard research diagnoses. A 2-stage screening process was used to identify cases in ACT. The Cognitive Abilities Screening Instrument (CASI)  is a cognitive test derived from the Mini-Mental State Examination (MMSE) . The CASI is administered to all ACT participants every 2 years. CASI scores ≤85 prompt a dementia evaluation; for comparison purposes, in the Honolulu Asia Aging Study (HAAS) the CASI cut point is 74. Informant, subject, or staff reports of cognitive difficulties also trigger evaluation. The 2nd stage diagnostic examination has two parts: neuropsychological testing and a neurological exam by a physician. Medical records are abstracted for standardized labs (complete blood counts, chemistry panel, B12, thyroid stimulating hormone) and neuroimaging. If any of these are unavailable in the prior year they are obtained. These data are used to complete standard DSM-IV diagnostic criteria for dementia and subtypes, NINCDS-ADRDA criteria for AD, and 3 sets of criteria for vascular dementia. The dementia neuropsychological battery includes tests of clock drawing, verbal fluency, Mattis Dementia Rating Scale, Boston naming, verbal paired associations and recall, logical memory and recall, Word List Memory, Constructional Praxis and recall, Trails A and B, and Information and Comprehension subtest items. All clinical data are reviewed at a consensus conference. These procedures have been used continuously over 23 years since the inception of the ADPR in 1986. ACT dementia and AD diagnoses have been used in many papers, including an incidence rate paper, and high-impact papers on exercise18, cholesterol19, statins20, and vitamins21.
Another outcome, diabetic retinopathy, was selected for funding through an ARRA supplement to mine the