rs12071951 (NDUFS5P2/RPL7P9): Schizophrenia GWAS Variant

Key takeaways

• rs12071951 sits near two pseudogenes (non-coding sequences that resemble genes), NDUFS5P2 and RPL7P9, and was examined in a Swedish genome-wide association study of schizophrenia and bipolar disorder.
• No individual variant reached genome-wide significance in the primary new sample of 1507 schizophrenia cases, 836 bipolar disorder cases, and 2093 controls.
• The alternate allele is linked to increased PTBP2 (polypyrimidine tract binding protein 2) expression in two brain regions and in testis, based on tissue expression data from 953 donors.
• Evidence for this locus is preliminary, drawn from a single study, with no replication data available for this specific variant.

What the research says A genome-wide association study (GWAS - a large-scale scan comparing genetic variants between people with and without a condition) of schizophrenia (SCZ) and bipolar disorder (BD) was conducted in a Swedish population comprising 1507 SCZ cases, 836 BD cases, and 2093 controls; no single-nucleotide polymorphisms (SNPs - positions in the genome where people differ by a single DNA letter) reached genome-wide significance in this new sample. A combined SCZ analysis (2111 cases and 2535 controls) identified a genome-wide significant signal in the major histocompatibility complex (MHC) region at rs886424 (P = 4.54 x 10^-8), a separate locus not involving this variant. Tissue expression data from 953 GTEx donors shows the alternate allele at this locus is associated with increased PTBP2 expression in spinal cord cervical and caudate basal ganglia brain regions, as well as in testis GTEx Portal.

Reported associations

• Schizophrenia (studied context): This variant was examined in a Swedish GWAS that included 1507 SCZ cases and 2093 controls; the study did not report genome-wide significant associations for individual SNPs in the new sample.
• Bipolar disorder (studied context): The same GWAS included 836 BD cases; no genome-wide significant individual SNP associations were reported for the new BD sample.
• PTBP2 expression, brain and testis: The alternate allele is linked to increased PTBP2 expression in spinal cord cervical, caudate basal ganglia, and testis tissues GTEx Portal.
• ENSG00000296873 expression, tibial artery: The alternate allele is linked to increased expression of an uncharacterized gene (ENSG00000296873) in tibial artery tissue GTEx Portal.

Evidence quality The only study in the provided evidence base is a single Swedish GWAS with a new sample of 1507 SCZ cases, 836 BD cases, and 2093 controls, and a combined SCZ sample of 2111 cases and 2535 controls. No genome-wide significant association (p below 5 x 10^-8, the conventional threshold for distinguishing real signals from chance when millions of variants are tested) was detected for individual SNPs in the new sample. The study found genome-wide significance only in the MHC region for SCZ and differential copy number variant (CNV, a type of structural DNA change) enrichment between SCZ and BD, but neither finding directly involves rs12071951. No independent replication of this specific variant is available in the provided material, placing the evidence at a preliminary, exploratory level. The GTEx eQTL data (from 953 donors, FDR below 0.05) represents a separate line of evidence about tissue-specific expression and does not itself constitute evidence for disease association.

Tissue-specific expression effects

• PTBP2: The alternate allele is associated with increased expression in two brain regions (spinal cord cervical and caudate basal ganglia) and in testis; the brain effects are larger than the testis effect GTEx Portal.
• ENSG00000296873: The alternate allele is associated with increased expression in tibial artery tissue GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.