Scientific Publications

Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder.

Publication TypeJournal Article
AuthorsBergen, SE, O'Dushlaine CT, Ripke S., Lee PH, Ruderfer DM, Akterin S., Moran JL, Chambert KD, Handsaker RE, Backlund L., Osby U., McCarroll S., Landen M., Scolnick EM, Magnusson PK, Lichtenstein P., Hultman CM, Purcell SM, Sklar P., and Sullivan PF
AbstractSchizophrenia (SCZ) and bipolar disorder (BD) are highly heritable psychiatric disorders with overlapping susceptibility loci and symptomatology. We conducted a genome-wide association study (GWAS) of these disorders in a large Swedish sample. We report a new and independent case-control analysis of 1507 SCZ cases, 836 BD cases and 2093 controls. No single-nucleotide polymorphisms (SNPs) achieved significance in these new samples; however, combining new and previously reported SCZ samples (2111 SCZ and 2535 controls) revealed a genome-wide significant association in the major histocompatibility complex (MHC) region (rs886424, P=4.54 × 10(-8)). Imputation using multiple reference panels and meta-analysis with the Psychiatric Genomics Consortium SCZ results underscored the broad, significant association in the MHC region in the full SCZ sample. We evaluated the role of copy number variants (CNVs) in these subjects. As in prior reports, deletions were enriched in SCZ, but not BD cases compared with controls. Singleton deletions were more frequent in both case groups compared with controls (SCZ: P=0.003, BD: P=0.013), whereas the largest CNVs (>500 kb) were significantly enriched only in SCZ cases (P=0.0035). Two CNVs with previously reported SCZ associations were also overrepresented in this SCZ sample: 16p11.2 duplications (P=0.0035) and 22q11 deletions (P=0.03). These results reinforce prior reports of significant MHC and CNV associations in SCZ, but not BD.Molecular Psychiatry advance online publication, 12 June 2012; doi:10.1038/mp.2012.73.
Year of Publication2012
JournalMolecular psychiatry
Date Published (YYYY/MM/DD)2012/06/12
ISSN Number1359-4184
DOI10.1038/mp.2012.73
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/22688191?dopt=Abstract