Study Report

Reference	Huang, J.,2010 PMID: 20713499
Citation	Huang, J., R. H. Perlis, et al. (2010). "Cross-disorder genomewide analysis of schizophrenia, bipolar disorder, and depression." Am J Psychiatry 167(10): 1254-1263.
Disease Type	Bipolar Disorder & Schizophrenia & Major Depressive Disorder
Study Design	case-control
Study Type	Genome-wide association study
Sample Size	schizophrenia (CATIE, genotyped:N=741), bipolar disorder (STEP-BD, genotyped:N=1,575), and major depressive disorder (STAR*D, genotyped: N=1,938) as well as from psychiatrically screened control subjects (NIMH-Genetics Repository:N=1,204)
SNP/Region/Marker Size	1,574,154 SNPs
Predominant Ethnicity
Population	STEP-BD,CATIE,STAR*D and NIMH collections

Statistical Method

Additional quality control for the combined genotypic data set was performed using PLINK.We fi rst computed a likelihood ratio statistic (the omnibus test statistic) from a multinomial logistic regression in which allele frequencies can vary for each sample (schizophrenia, bipolar I disorder, bipolar II disorder, major depressive disorder, and control) relative to a null model in which allele frequencies are the same across all groups.We then identified the best-fit model based on the Bayesian information criterion.

Result Summary

RESULTS: The strongest result was seen for a single nucleotide polymorphism near the adrenomedullin (ADM) gene (rs6484218), with the best-fitting model indicating that the effect was specific to bipolar II disorder. Findings also revealed evidence suggesting that several genes may have effects that transcend clinical diagnostic boundaries, including variants in NPAS3 that showed pleiotropic effects across schizophrenia, bipolar disorder, and major depressive disorder. CONCLUSIONS: This study provides the first genomewide significant evidence implicating variants near the ADM gene on chromosome 11p15 in psychopathology, with effects that appear to be specific to bipolar II disorder. Although genomewide significant evidence of cross-disorder effects was not detected, the results provide evidence that there are both pleiotropic and disorder-specific effects on major mental illness and illustrate an approach to dissecting the genetic basis of mood and psychotic disorders that can inform future large-scale cross-disorder GWAS analyses.