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NESDA and GAIN

About GAIN
(quotations from the paper that appeared in Nature Genetics 2007)
The Genetic Association Information Network (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. GAIN is established to investigate the genetic basis of common diseases through a series of collaborative genome-wide association studies. Genome-wide association studies hold tremendous promise for unraveling the genetics of complex diseases, but the genomics community faces enormous challenges in analyzing data sets of billions of genotypes, distinguishing the small number of true positive associations and following their leads to causative variants and effective interventions. GWA studies, almost regardless of the trait(s) under study, present many common challenges in analysis and interpretation that are likely to have common solutions. These solutions, and the potential for combining phenotype and genotype data across studies to enhance statistical power, are best developed through collaborative approaches such as GAIN, in which significant data resources can be developed and made available for the collective benefit of the entire scientific community. Sharing these data outside the GAIN collaborative group, and encouraging the scientific community to use these data responsibly and participate actively in their analysis, should speed the dentification of variants related to complex diseases and the development of effective new treatments. In early 2006, the FNIH solicited DNA samples from existing studies worldwide for genotyping by GAIN in a GWA study. Applications underwent a multistage review process, including an administrative review for adherence to the application format and submission requirements, a scientific peer review assessing the likelihood of identifying important genotype-phenotype ssociations from the study, and a programmatic and technical review for quality and ease of use of the proposed data set, limitations on research use or data sharing, public health significance and diversity of represented populations.
The six studies recommended to, and approved by, the FNIH Board of Directors included four studies of mental health disorders (attention deficit hyperactivity disorder (ADHD), bipolar I disorder (major depression) and schizophrenia) and one study each of diabetic nephropathy and psoriasis. The prominent representation of mental health studies reflects the large number and high quality of such applications submitted to GAIN. Perlegen Sciences and the Broad Institute's Genetic Analysis Platform are performing genotyping. Perlegen Sciences is using a prietary, high-density oliogunucleotide array-based platform with roughly 480.000 SNPs for the ADHD, MDD and psoriasis studies. The genotype data generated for each study sample, plus de-identified, coded phenotype and exposure data, will be deposited in a controlled access section of the GAIN database.
For more information about GAIN read the entire paper New models of collaboration in genome-wide association studies: the Genetic Association Information Network and the supplement that appeared in Nature Genetics, august 2007, or visit the GAIN website at www.fnig.org

NESDA and GAIN
The Netherlands Twin Register (NTR) and the Netherlands Study of Depression and Anxiety (NESDA), together with colleagues from the CNCR (Center for Neurogenomics and Cognitive Research, VU University Medical Center) and the University of Carolina (Patrick Sullivan), wrote an application for genotyping their DNA samples by GAIN to get a better insight into the molecular genetics of Major Depression Disorder. In October 2006 the approval of their application was announced by Francis Collins, leader of the Humane Genome Project. 1860 cases from the NESDA study (1703 with major depression and 157 controls) and 1860 (mainly) controls from the NTR study have received a genome-wide scan. The genotyping was complete at October 9, 2007.
NESDA and NTR have 9 months for submitting abstracts and publications and to make presentations about the data and samples they contributed to GAIN. During this period, approved users have access to the data set but agree not to submit or presentation or publication any results derived from it. At the end of the 9-month period, approved users may publicly discuss and submit papers for publication on GAIN data for any purpose consistent with the politics and practices of GAIN, the FNIH and NIH.

All cases in both NESDA and NTR have been assessed using the CIDI, an internationally accepted structured psychiatric diagnostic interview. The CIDI yields lifetime diagnoses of DSM-IV MDD (Major Depressive Disorder) along with exclusionary conditions (e.g. history of stroke or moderate/severe drug or alcohol dependence). Age of onset is obtained (which may identify subgroups of MDD with greater heritability) along with data on clinically important comorbid disorders. For those who screen positive for lifetime MDD in NESDA, psychiatrists or clinical psychologists affiliated with NESDA conduct semi-structured clinical evaluations in order to confirm that all inclusion and exclusion criteria are satisfied. In the NTR, longitudinal assessments are available and inclusion as a control requires low depressive symptom scores at multiple time points.

NESDA investigators who would like to use the genetic data for reseach purposes, should fill out a data-analysis plan. If only NESDA participants are included in the genetic analysis, one should fill out a NESDA amanlysis plan. If also NTR data are required, one should fill out the GWA-gain analysis plan.

Downloads
- GAIN MDD project description
- Form GWA-gain analysis plan

- Form NESDA-analysis plan
- Publication protocol for GWA data of the NESDA and NTR sample. (Dutch version)

More information about the Netherlands Twin register can be found at www.tweelingenregister.org

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