PDF《Association Information Network》

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200 7 Nature Publishing Group http://www.

nature.com/naturegenetics New models of collaboration in genome- wide association studies: the Genetic Association Information Network The GAIN Collaborative Research Group The Genetic Association Information Network (GAIN) is a public-private partnership established to investigate the genetic basis of common diseases through a series of collaborative genome- wide association studies. GAIN has used new approaches for project selection, data deposition and distribution, collaborative analysis, publication and protection from premature intellectual property claims. These demonstrate a new commitment to shared scientific knowledge that should facilitate rapid advances in understanding the genetics of complex diseases. Genome-wide association (GWA) studies of large numbers of individuals genotyped for hundreds of thousands of common genetic variants have now convincingly been shown to be effective in identifying genes related to health and disease1C10. The growing under- standing of genome variation provided by the International HapMap Consortium11 and continued major advances in genotyping technology12 have together made it possible to conduct high-throughput,cost-effective GWA studies in large numbers of individuals with detailed information on phenotypic traits and environmental exposures. The resulting data will be used to identify genetic variants poten- tially related to health and disease,to assess the prevalence of these variants in large and diverse samples and to examine possible modifiers of gene-disease relationships. Many GWA studies thus far have focused on a single phenotype, such as diabetes or breast cancer4C9, or on closely related pheno- types, such as ulcerative colitis and Crohn'

s disease13, within a single study. However, the pressing need for replication of initial asso- ciations14 and the opportunities for develop- A full list of participating authors and research groups is given at the end of this paper. e-mail: [email protected] Published online

29 August 2007;

doi:10.1038/ ng2127 ing common methods across GWA studies have led to the formation of networks of col- laborative GWA studies involving different study samples and multiple phenotypes. The Wellcome Trust Case Control Consortium (WTCCC) is one such network;

its pioneering effort on seven complex diseases and common controls has proven the power and potential of this approach10. GAIN is another, currently involving six different studies with case-control or family trio designs. Such efforts to develop robust,common approaches to study selection, genotyping, quality control, data analysis and data sharing, as well as cross-study analyses of common phenotypes, common controls and genotyping artifacts,are topics of considerable current interest. GAIN is a public-private partnership between the Foundation for the National Institutes of Health (FNIH), the US National Institutes of Health (NIH) and partners in the academic and private sectors. The FNIH was established by the US Congress to support the mission of NIH;

it works to advance scientific research by linking the generosity of private- sector donors and partners to programs that support the NIH mission. GAIN involves four private-sector partners at present, includ- ing the founding lead partner, Pfizer, as well as Affymetrix, Perlegen Sciences and Abbott, and one academic-sector partner, the Eli and Edythe L.Broad Institute of MIT and Harvard. Commitments from these partners have sup- ported the initial development of GAIN and the genotyping and data distribution for up to 18,000 samples. Subsequent commitments will be sought to support future GWA studies by GAIN and to extend its infrastructure for broader use. The design and implementation of GAIN has been directed by a series of guiding princi- ples (Box1) that will be adhered to throughout the life of the project. GAIN will release data as broadly and rapidly as possible, with equal opportunity for access by all users who agree to protect the confidentiality of study participants and to respect the intellectual investment of the investigators contributing data and samples to GAIN. Here we describe the selection and characteristics of the first six GAIN studies, as well as the design, policies, protections and implementation of GAIN as a whole. Selection and characteristics of initial GAIN studies In early 2006,the FNIH solicited DNA samples from existing studies worldwide for genotyp- ing by GAIN in a GWA study (http://www.fnih. org/GAIN/Instructions_for_Applicants.shtml;