rs10949662 (PTPRN2): Schizophrenia and Cognition
Key takeaways
- rs10949662 near PTPRN2 has been examined in large GWASes covering schizophrenia, intelligence, education, and cognitive function, some enrolling over 1 million people.
- The schizophrenia study included up to 76,755 cases and 243,649 controls and found 287 significant genetic loci, all concentrated in brain neurons.
- Polygenic scores from cognitive function research explain up to 4.3% of variance in general cognitive ability, with each individual variant contributing only a tiny fraction.
- In testicular tissue, this variant is linked to lower expression of a nearby gene, but no brain-tissue expression effects were found in the available data.
- All four relevant studies enrolled predominantly European-ancestry participants, so findings may not apply equally to all ancestry groups.
Key takeaways
- rs10949662 near PTPRN2 (Protein Tyrosine Phosphatase Receptor Type N2) has been examined in large genome-wide studies covering schizophrenia, intelligence, educational attainment, and cognitive function, some enrolling over 1 million people.
- The schizophrenia study associated with this locus enrolled up to 76,755 cases and 243,649 controls and found 287 significant genetic loci, all concentrated in brain neurons.
- Polygenic scores from cognitive function research explain up to 4.3% of variance in general cognitive ability, with each individual variant contributing only a tiny fraction.
- In testicular tissue, rs10949662 is linked to lower expression of a nearby gene (ENSG00000231515), but no brain-tissue expression effects appear in the available data.
- All four relevant studies enrolled predominantly European-ancestry participants, so findings may not apply equally to all ancestry groups.
What the research says A genome-wide association study (GWAS) of schizophrenia, a psychiatric condition associated with altered perception and cognition, enrolled up to 76,755 affected individuals and 243,649 controls, identifying 287 genomic loci where associated variants concentrate in genes expressed in CNS neurons rather than other tissue types PMID 35396580. A multi-trait analysis (MTAG) combining GWASes of intelligence and educational attainment across an effective sample of 248,482 individuals found 187 loci, with implicated genes enriched for neurogenesis (new neuron formation), myelination (the insulating sheath around nerve fibres), and synaptic activity PMID 31980815. A GWAS of educational attainment in approximately 1.1 million individuals identified 1,271 genome-wide significant variants with a median per-allele effect of about 1.7 weeks of schooling, implicating genes in brain development and neuron-to-neuron communication PMID 30038396.
Reported associations
- Schizophrenia: This locus was examined in the largest schizophrenia GWAS to date, which identified 287 genome-wide significant loci in up to 76,755 cases and 243,649 controls; SNP-based heritability (the share of risk variance explained by measured common genetic variants) in the European-ancestry subsample was approximately 0.24 (SE 0.007), with associations concentrated in genes expressed in excitatory and inhibitory CNS neurons PMID 35396580.
- General intelligence: A multi-trait analysis combining GWASes of intelligence and educational attainment in a functional sample of 248,482 individuals identified 187 genome-wide significant loci, with implicated genes enriched for neurogenesis, myelination, and synaptic regulation PMID 31980815.
- Educational attainment: A GWAS of years of schooling in approximately 1.1 million individuals identified 1,271 independent genome-wide significant SNPs; median per-allele effect was about 1.7 weeks of schooling (5th-95th percentile: 1.1-2.6 weeks), and polygenic scores explained approximately 11-13% of educational attainment variance in independent samples PMID 30038396.
- General cognitive function: A GWAS in 300,486 individuals aged 16-102 drawn from the CHARGE and COGENT consortia and UK Biobank identified 148 genome-wide significant loci, including variants linked to neurodegenerative and neurodevelopmental conditions; polygenic scores explained up to 4.3% of variance in general cognitive function in independent samples PMID 29844566.
Evidence quality The four studies providing context for this locus span sample sizes from 300,486 participants for general cognitive function PMID 29844566 to over 1.1 million for educational attainment PMID 30038396, placing them among the largest genetic studies of their respective traits. The schizophrenia GWAS PMID 35396580 used a two-stage design with a genome-wide significance threshold of p < 5x10^-8 and included participants of European, East Asian, African-American, and Latino ancestry. The intelligence MTAG study PMID 31980815 leveraged a genetic correlation of rg = 0.70 between intelligence and educational attainment to boost statistical power, growing the effective sample from 199,242 to 248,482 participants. The educational attainment study PMID 30038396 conducted within-family analyses in 22,135 sibling pairs to probe robustness against population stratification bias. All four studies enrolled predominantly European-ancestry individuals, which is a meaningful limitation for applying results to other ancestry groups. No directly conflicting findings between the four studies are evident in the provided evidence. The biological connection between the testis expression effect and the brain-related GWAS associations is not established by the available data.
Tissue-specific expression effects
- ENSG00000231515: GTEx v11 data (953 donors) shows that rs10949662 is associated with reduced expression of this gene in testicular tissue at high statistical significance (p = 1.9e-18). No eQTL associations in brain or other central nervous system tissues are present in the available data for this variant. GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is PTPRN2?
PTPRN2 is the gene near rs10949662. The studies associated with this variant do not detail its specific biological function, but the locus falls within genomic regions examined in research on brain-related traits including schizophrenia and cognitive function.
Is rs10949662 linked to schizophrenia?
This variant was examined in the largest schizophrenia GWAS to date, which enrolled up to 76,755 cases and 243,649 controls and identified 287 significant genomic loci all concentrated in brain neurons. Whether rs10949662 itself independently reaches genome-wide significance for schizophrenia risk is not explicitly confirmed in the available study text.
Can rs10949662 predict intelligence or educational outcomes?
This variant contributes to polygenic scores for intelligence and educational attainment alongside thousands of other variants. Such scores explain around 11-13% of educational attainment variance and up to 4.3% of cognitive function variance. No single variant, including this one, has strong standalone predictive power.
What does the GTEx expression data show for rs10949662?
GTEx v11 data from 953 donors shows that rs10949662 is associated with reduced expression of a nearby gene (ENSG00000231515) in testicular tissue. No eQTL effects in brain or other central nervous system tissues are present in the available GTEx data for this variant.
How large were the studies examining this variant?
The studies range from approximately 300,000 participants for general cognitive function to over 1.1 million for educational attainment. The schizophrenia study included up to 76,755 cases and 243,649 controls. These are among the largest genetic studies ever conducted for their respective traits.