rs11632125 (C15orf32/LINC00930): Schizophrenia Risk

Key takeaways

• rs11632125 sits in a genomic region spanning the C15orf32 gene (chromosome 15 open reading frame 32) and LINC00930 (a long intergenic non-coding RNA), identified among hundreds of locations in the genome linked to schizophrenia risk
• The association comes from one of the largest genetic studies of schizophrenia ever conducted, analysing up to 76,755 people with the condition and 243,649 controls across four ancestry groups
• Genetic risk signals across all identified loci were concentrated in neurons of the central nervous system, not in other tissues or cell types
• Common genetic variants across the genome together account for roughly 24% of the inherited variation in schizophrenia susceptibility in people of European ancestry

What the research says A large-scale genome-wide association study (GWAS, a method that scans hundreds of thousands of genetic markers across the genome to find variants more common in people with a given condition) identified 287 distinct genomic loci associated with schizophrenia, including the C15orf32 - LINC00930 region on chromosome 15, in a sample of up to 76,755 cases and 243,649 controls drawn from European, East Asian, African-American, and Latino ancestries. Associations across this and all other identified loci were concentrated in genes expressed in central nervous system neurons - both excitatory (signal-activating) and inhibitory (signal-dampening) types - but not in other tissues or cell types. The SNP-based heritability (the proportion of variation in schizophrenia liability explained by all measured common genetic variants) was estimated at 0.24 in the European ancestry sample, and polygenic risk scores derived from the full GWAS explained a median of 7.3% of variance in liability across cohorts.

Reported associations

• Schizophrenia: This locus was among 287 distinct genomic regions reaching genome-wide significance in the primary GWAS; the specific effect size and allele frequency for rs11632125 individually were not reported in the available study excerpts

Evidence quality The schizophrenia association for this locus derives from one of the largest GWAS of any psychiatric disorder to date, combining 90 cohorts in a primary analysis (74,776 cases and 101,023 controls) and supplementing with data from deCODE Genetics in an extended analysis totalling up to 76,755 cases and 243,649 controls. The primary analysis identified 313 independent SNPs (linkage disequilibrium r2 < 0.1, a measure of how independently variants are inherited from one another) exceeding a genome-wide significance threshold of p < 5x10-8 across 263 distinct loci; the extended analysis yielded 342 independent SNPs across 287 loci. Samples spanned four ancestry groups (74.3% European, 17.5% East Asian, 5.7% African-American, 2.5% Latino). No conflicting studies were provided. The specific p-value and effect estimate for rs11632125 individually were not available in the provided study text, so the relative strength of this locus within the broader findings cannot be assessed from the available material.

Lifestyle considerations No lifestyle considerations on file for this variant.