title: Phenotype harmonization and cross-study collaboration in GWAS consortia: the GENEVA experience.
abstract: Genome-wide association study (GWAS) consortia and collaborations formed to detect genetic loci for common phenotypes or investigate gene-environment (G*E) interactions are increasingly common. While these consortia effectively increase sample size, phenotype heterogeneity across studies represents a major obstacle that limits successful identification of these associations. Investigators are faced with the challenge of how to harmonize previously collected phenotype data obtained using different data collection instruments which cover topics in varying degrees of detail and over diverse time frames. This process has not been described in detail. We describe here some of the strategies and pitfalls associated with combining phenotype data from varying studies. Using the Gene Environment Association Studies (GENEVA) multi-site GWAS consortium as an example, this paper provides an illustration to guide GWAS consortia through the process of phenotype harmonization and describes key issues that arise when sharing data across disparate studies. GENEVA is unusual in the diversity of disease endpoints and so the issues it faces as its participating studies share data will be informative for many collaborations. Phenotype harmonization requires identifying common phenotypes, determining the feasibility of cross-study analysis for each, preparing common definitions, and applying appropriate algorithms. Other issues to be considered include genotyping timeframes, coordination of parallel efforts by other collaborative groups, analytic approaches, and imputation of genotype data. GENEVA's harmonization efforts and policy of promoting data sharing and collaboration, not only within GENEVA but also with outside collaborations, can provide important guidance to ongoing and new consortia.
authors.affiliation: Collaborative Health Studies Coordinating Center, Department of Biostatistics, University of Washington, Seattle, Washington 98115, USA. siirib@u.washington.edu
authors.forename: Siiri N
authors.initials: SN
authors.lastname: Bennett
authors.forename: Neil
authors.initials: N
authors.lastname: Caporaso
authors.forename: Annette L
authors.initials: AL
authors.lastname: Fitzpatrick
authors.forename: Arpana
authors.initials: A
authors.lastname: Agrawal
authors.forename: Kathleen
authors.initials: K
authors.lastname: Barnes
authors.forename: Heather A
authors.initials: HA
authors.lastname: Boyd
authors.forename: Marilyn C
authors.initials: MC
authors.lastname: Cornelis
authors.forename: Nadia N
authors.initials: NN
authors.lastname: Hansel
authors.forename: Gerardo
authors.initials: G
authors.lastname: Heiss
authors.forename: John A
authors.initials: JA
authors.lastname: Heit
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Kang
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Kittner
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: William
authors.initials: W
authors.lastname: Lowe
authors.forename: Mary L
authors.initials: ML
authors.lastname: Marazita
authors.forename: Kristine R
authors.initials: KR
authors.lastname: Monroe
authors.forename: Louis R
authors.initials: LR
authors.lastname: Pasquale
authors.forename: Erin M
authors.initials: EM
authors.lastname: Ramos
authors.forename: Rob M
authors.initials: RM
authors.lastname: van Dam
authors.forename: Jenna
authors.initials: J
authors.lastname: Udren
authors.forename: Kayleen
authors.initials: K
authors.lastname: Williams
mesh_terms: D016022:Case-Control Studies; D003299:Cooperative Behavior; D003625:Data Collection; D003627:Data Interpretation, Statistical; D030541:Databases, Genetic; D004777:Environment; D005260:Female; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data*; D005838:Genotype; D006801:Humans; D008297:Male; D017720:Molecular Epidemiology / Q000706:statistics & numerical data; D010641:Phenotype; D018401:Sample Size