rs10148671 (LINC02327): Schizophrenia and Behavior GWAS

Key takeaways

• Multiple large-scale schizophrenia GWAS studies, including the largest ever with 76,755 cases and 243,649 controls, form the primary evidence base for this variant
• rs10148671 sits near LINC02327 and LINC02326, two non-coding RNA genes that do not produce protein, making biological interpretation challenging
• Genetic signals in this region replicate across European, Chinese, Japanese, and Ashkenazi Jewish populations
• Secondary associations span externalizing behaviors (substance use, ADHD, risk-taking) from a multivariate GWAS of approximately 1.5 million people
• All reported associations are statistical; no functional mechanism has been established for this locus

What the research says rs10148671 falls near LINC02327 and LINC02326, both annotated as long intergenic non-coding RNAs (lincRNAs) - RNA molecules transcribed from the genome that do not produce protein; their regulatory roles remain poorly characterized. The primary evidence base spans a schizophrenia GWAS meta-analysis involving up to 76,755 cases and 243,649 controls that identified 287 genome-wide significant loci, alongside replication studies in Chinese (n = 36,180), Japanese, and Ashkenazi Jewish cohorts. A multivariate GWAS of externalizing traits in approximately 1.5 million people, a UK Biobank lifetime smoking GWAS (N = 394,718), and a case-case GWAS across eight psychiatric disorders (CC-GWAS) round out the evidence base.

Reported associations

• Schizophrenia (European-led meta-analysis): The largest analysis included 76,755 cases and 243,649 controls and identified 287 genome-wide significant loci; SNP-based heritability was 0.24 (SE 0.007) in the European subsample, and polygenic risk scores explained a median of 7.3% of variance in schizophrenia liability (genome-wide significant SNPs only: 2.4%)
• Schizophrenia (Chinese/trans-ancestry): A Chinese GWAS (n = 36,180 individuals, combined with PGC data) identified 113 genome-wide significant loci total (30 novel); approximately 95% of European-identified risk alleles were overrepresented in Chinese cases, with about 75% remaining genome-wide significant in the trans-ancestry analysis
• Schizophrenia (Japanese population): A two-stage Japanese GWAS (discovery: 1,940 cases, 7,408 controls; replication: 4,071 cases, 54,479 controls) found a genetic correlation of rg = 0.58 between Japanese and European schizophrenia signals, indicating partial cross-ancestry overlap
• Schizophrenia (Ashkenazi Jewish population): A combined US and Israeli Ashkenazi Jewish sample (1,505 cases, 2,145 controls) showed strong polygenic inheritance (SNP-heritability = 0.39, P = 0.00046) but did not yield independent genome-wide significant associations; the strongest AJ-specific signals were in the 22q11.2 region
• Cross-disorder psychiatric differentiation: CC-GWAS applied to eight psychiatric disorders identified 196 case-case loci, including 72 not detected by standard case-control methods; two CC-GWAS-specific loci implicate KLF6 and KLF16, genes linked to neurite outgrowth and axon regeneration, and results replicated in independent datasets
• Externalizing traits (substance use, ADHD, risk-taking): A multivariate GWAS of approximately 1.5 million participants identified more than 500 loci for shared externalizing liability; polygenic scores predicted opioid use disorder, suicide attempts, HIV infections, criminal convictions, and unemployment among outcomes not directly included in the GWAS
• Lifetime smoking behavior: A UK Biobank GWAS (N = 394,718) examined smoking behavior with and without adjustment for educational attainment; SNP-based heritability was 9.2% unadjusted and 7.2% after statistically removing the educational attainment component, demonstrating that part of smoking genetics overlaps with educational propensity genetics

Evidence quality The schizophrenia evidence is among the best-powered in psychiatric genetics. The primary meta-analysis exceeded 76,000 cases and 243,000 controls, was extended with deCODE Genetics data (1,979 cases, 142,626 controls), and yielded 287 independently significant loci replicated in a two-stage design. Cross-ancestry replication in Chinese (n = 36,180) and Japanese populations (combined n exceeding 60,000) increases confidence in the broad relevance of identified signals, though the Japanese-European genetic correlation was partial (rg = 0.58), indicating some population-specific variation. The Ashkenazi Jewish cohort (approximately 3,650 individuals total) was underpowered for independent genome-wide discovery but contributes converging polygenic evidence. The externalizing GWAS draws on approximately 1.5 million individuals across 11 correlated phenotypes; because the analysis is multivariate, individual-locus contributions reflect shared liability across externalizing traits rather than disorder-specific effects. The smoking GWAS demonstrates that a non-trivial portion of smoking genetics (SNP-heritability dropping from 9.2% to 7.2%) overlaps with educational attainment genetics, complicating the interpretation of individual loci in that signal. No functional studies of rs10148671 in the LINC02327/LINC02326 region are reported in the provided evidence base, and no causal mechanism has been established at this locus.

Lifestyle considerations No lifestyle considerations on file for this variant.