nif:isString
|
-
All protocols and sample collections were approved by the IRB of the Massachusetts General Hospital and all data were analysed anonymously. The STAR*D cohort [16] has been extensively used in many genetic studies and has been thoroughly documented [17]. Lifetime history of suicide attempts was assessed at the initial study visit by the study clinician and suicidal behavior was not exclusionary for the initial STAR*D patient recruitment, provided the patient did not require hospitalization [18]. Genotyping for the STAR*D cohort utilized the Affymetrix GeneChip Human Mapping 500 K Array Set and the Affymetrix Human SNP Array 5.0 [19]. Genotypes for samples run on the Affymetrix 500 K Array (n = 969) were called using the BRLMM algorithm, and those analyzed on Affymetrix Array 5.0 (n = 979) were called using the BRLMM-P algorithm. Additional QC was performed using PLINK [20], where individuals or SNPs were excluded with total call-rates <95%, SNPs with call rates <98%, individuals with minor allele frequencies <1%, or out of Hardy-Weinberg equilibrium (p<1×10−6). We imputed missing genotypes using MACH and retained SNPs with r2>0.8. Eleven subjects were excluded due to missing clinical data resulting in a final dataset of 1, 262. CNVs were identified using Birdseye [21], which identifies CNVs by integrating intensity data from neighboring probes using a hidden Markov model (HMM) on a per- individual basis. Performance is dependent on a number of factors including SNP and copy number probe density, mean intra-individual probe variance and CNV frequency. For each CNV a LOD score was generated that describes the likelihood of the CNV relative to no CNV over the given interval. All CNV analysis were performed in PLINK and only those CNVs present in less than 10% of the total sample were used for analysis. Secondary controls for the current study came from the Database of Genomic Variants (http://projects.tcag.ca/variation/), a database of over 100, 000 CNVs from over 40 studies. While these studies do not explicitly screen for mood disorders, only controls from these studies are in the database.
|