The gene, environment association studies consortium (GENEVA): maximizing the knowledge obtained from GWAS by collaboration across studies of multiple conditions

Abstract

Genome-wide association studies (GWAS) have emerged as powerful means for identifying genetic loci related to complex diseases. However, the role of environment and its potential to interact with key loci has not been adequately addressed in most GWAS. Networks of collaborative studies involving different study populations and multiple phenotypes provide a powerful approach for addressing the challenges in analysis and interpretation shared across studies. The Gene, Environment Association Studies (GENEVA) consortium was initiated to: identify genetic variants related to complex diseases; identify variations in gene-trait associations related to environmental exposures; and ensure rapid sharing of data through the database of Genotypes and Phenotypes. GENEVA consists of several academic institutions, including a coordinating center, two genotyping centers and 14 independently designed studies of various phenotypes, as well as several Institutes and Centers of the National Institutes of Health led by the National Human Genome Research Institute. Minimum detectable effect sizes include relative risks ranging from 1.24 to 1.57 and proportions of variance explained ranging from 0.0097 to 0.02. Given the large number of research participants (N > 80,000), an important feature of GENEVA is harmonization of common variables, which allow analyses of additional traits. Environmental exposure information available from most studies also enables testing of gene-environment interactions. Facilitated by its sizeable infrastructure for promoting collaboration, GENEVA has established a unified framework for genotyping, data quality control, analysis and interpretation. By maximizing knowledge obtained through collaborative GWAS incorporating environmental exposure information, GENEVA aims to enhance our understanding of disease etiology, potentially identifying opportunities for intervention.

Mayo Genome Consortia: A Genotype-Phenotype Resource for Genome-Wide Association Studies With an Application to the Analysis of Circulating Bilirubin Levels

“…4,5,9,10 The UGT1A cluster encodes 9 transferase genes (UGT1A* 1, 3,4,5,6,7,8,9,10), of which 8 are known active gene transcripts. All of the UGT1A proteins are identical in the amino acid sequence encoded by exons 2 through 5 with unique alternate first exons.…”

“…2 The GENEVA (Gene Environment Association Studies) Study of Venous Thromboembolism of the National Human Genome Research Institute enrolled consecutive Mayo Clinic outpatients with objectively diagnosed deep venous thrombosis and/or pulmonary embolism who resided in the upper Midwest and had been referred by a Mayo Clinic physician to the Mayo Clinic Special Coagulation Laboratory or to the Mayo Clinic Thrombophilia Center. 6 A deep venous thrombosis or pulmonary embolism was categorized as objectively diagnosed (1) when it was confirmed by venography or pulmonary angiography or via a pathology examination of a thrombus removed at surgery or (2) if findings on at least 1 noninvasive test (compression duplex ultrasonography, lung scan, computed tomography, magnetic resonance imaging) were positive. Persons with venous thromboembolism related to active cancer were excluded.…”

Contrasting genetic architectures in different mouse reference populations used for studying complex traits

“…Large-scale international efforts are underway to dissect the genetics of these common conditions (Cornelis et al 2010;Sullivan 2010;Ehret et al 2011;Rivas et al 2011;Yang et al 2012). However, of the thousands of significant associations between genetic variants and complex traits or disease, most account for only a modest portion of overall trait variability (Visscher et al 2012;Robinson et al 2014).…”

Measuring alcohol consumption for genomic meta-analyses of alcohol intake: opportunities and challenges

“…Thus, depending on the goals of a study, measures of alcohol consumption can be collected by using food-frequency questionnaires, from medical charts, via self-report in case-control studies of health-related outcomes, and from interviews in studies for addiction and other psychiatric disorders. To illustrate this remarkable variation in the assessment of alcohol consumption, representative alcohol-consumption measures from individual studies of the GENEVA Consortium are shown in Table 1 (46,47).…”