Department of Veterans Affairs Cooperative Studies Program genetic linkage study of schizophrenia: Ascertainment methods and sample description

Abstract

To help clarify the genetics of schizophrenia, the Department of Veterans Affairs Cooperative Studies Program has completed data collection for a genetic linkage study of schizophrenia. This article describes the methodological details of the data collection. Subsequent articles will describe the results of our genome scan, which is now in progress. The data collection protocol included the Diagnostic Interview for Genetic Studies, the Family Interview for Genetic Studies, a review of medical records, and the collection of blood for transformation into lymphoblast cell lines. Among relatives of schizophrenic probands, we assessed auditory attention and verbal memory with neuropsychological tests. Among the 166 families ascertained for the study, 143 had a single affected sib-pair, 17 had three affected siblings, one had five affected siblings and five had two sets of affected siblings. There was a total of 216 affected sib-pairs in these families. Using the n-1 rule, these families contain 188 independent affected sib-pairs.

Visualization of Haplotype Sharing Patterns in Pedigree Samples

“…An aim of the study was to identify a few subjects for further genomewide sequencing to find a susceptibility variant in a region with evidence of linkage. Pedigree samples from previous studies [29,30] were genotyped with 4,604 genomewide SNP markers spaced at 1 cM intervals, on average, selected from the Illumina HumanLinkage-24 BeadChip array. Our nonparametric and parametric multipoint linkage analyses [1,3,31] identified a pedigree of interest that has evidences for linkage on chromosomes 14 and 19 genotyped for 185 and 100 markers, respectively.…”

Evidence for involvement of GNB1L in autism

“…One hundred fifty five cases were European-Americans and 116 were African-American. For the current project, all cases met DSM-IV criteria for schizophrenia using the Diagnostic Interview for Genetic Studies and related instruments, as described in previous publications [Tsuang et al, 2000; Calkins et al, 2007]. …”

Genome scan of schizophrenia families in a large Veterans Affairs Cooperative Study sample: Evidence for linkage to 18p11.32 and for racial heterogeneity on chromosomes 6 and 14

“…Tsuang et al [2000] provide a detailed description of the study methodology and description of the sample. The ascertainment of pedigrees began with the identification of ill probands having at least one biological relative meeting DSM‐III‐R criteria for the proband selection diagnoses: schizophrenia and schizoaffective disorder, depressed.…”

“…DSM‐III‐R diagnoses were made independently at each site by two senior psychiatrist or psychologist investigators with clinical and research experience in the diagnosis of psychotic patients. We achieved high inter‐rater agreement on the ascertainment diagnoses as indicated by a kappa coefficient of 0.89 [Tsuang et al, 2000].…”

“…We previously reported initial results for chromosomes 6, 13, and 15 from a genome scan of 166 schizophrenia families collected through the Department of Veterans Affairs Cooperative Studies Program [Tsuang et al, 2000, 2001; Faraone et al, 2002b; Skol et al, 2003]. A summary and highlights of the completed genome scan are presented herein along with tests for racial heterogeneity at our most interesting linkage signals.…”