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Summary Background:Schizophrenia is a relatively common disorder, with a lifetime prevalence of about 1%. Family history is the most important risk factor for schizophrenia, consistent with a genetic contribution to its etiology. Recent human genetic studies reported that some common variants located within BCL9 are associated with schizophrenia in the Chinese population, but not associated with bipolar disorder in the Caucasian population. Methods: Single nucleotide variant (SNP) prioritization sample was comprised of 575 patients with schizophrenia and 564 healthy controls with no personal or family history of psychiatric illness. For SNP association analysis, we used an independent Japanese sample set (replication sample) comprising 1464 cases and 1171 controls. For the analysis of cognitive performance, we investigated 115 cases and 87 controls using Continuous Performance Test (CPT-IP) and the Wisconsin Card Sorting Test Keio version (WCST). Meta-selectanalysis was performed using a combined Japanese total sample (N=3735) and a Chinese sample from a previous study. Results: In the replication sample set, we did not detect any association in 2 SNPs (rs672607 and rs10494252) and schizophrenia. Meta-analysis of rs672607 showed significant association (p-value 0.012, odds ratio 0.855). There was a significant (p<0.01) difference between the A/A and G carrier group of rs672607 in CPT mean d’ (p=0.0092). Conclusions: We were able to detect evidence for an association between rs672607 in BCL9 and schizophrenia in the meta-analysis of Japanese and Chinese populations. Additionally, this common variant may affect cognitive performance, as measured by the CPT-IP in schizophrenia patients. Kratak sadržaj Uvod: Sizofrenija je relativno čest poremećaj, sa rasprostra- njenošču od oko 1% u ukupnoj populaciji. Porodična istorija bolesti predstavlja najvažniji faktor rizika za nastanak šizofre- nije, što je u skladu sa genetickom osnovom njene etiologije. Nedavne genetičke študije pokazuju da su neke uobičajene varijante u okviru gena BCL9 u vezi sa šizofrenijom u kineskoj populaciji, ali ne i sa bipolarnim poremečajem u populaciji belaca. Metode: Uzorci za analizu tačkastih polimorfizama (SNP) potiču od 575 pacijenata sa šizofrenijom i 564 zdravih kon- trolnih subjekata bez lične ili porodične istorije psihijatrij- skih oboljenja. Za SNP analizu koriščen je nezavisni japanski set uzorak (replikacioni uzorak) koji sadrži 1464 slučaja bolesti i 1171 kontrolu. Za analizu kognitivnih funkcija, ispi- tivali smo 115 slučajeva bolesti i 87 kontrolnih slučajeva, koriščenjem kontinualnog testa funkcija (CPT-IP) i Wisconsin Card Sorting testa, Keio verzije (WCST). Metaanaliza je uradena koriščenjem kombinovanog japanskog ukupnog uzorka (N = 3735) i kineskog uzorka iz prethodne študije. Rezultati: U replikacionom uzorku nije otkrivena nikakva veza izmedu 2 SNP-a (rs672607 i rs10494252) i šizofrenije. Metaanaliza rs672607 je pokazala njegovu značajnu pove- zanost sa šizofrenijom (p-vrednost 0,012, 0|,855 odds ratio). Utvrdená je značajna (p<0,01) razlika izmedu A/A i G grupe nosilaca rs672607 u CPT srednjoj vrednosti d' (p=0,0092). Zaključak: Dokazana je veza izmedu rs672607 u genu BCL9 i šizofrenije u metaanalizi japanske i kineske populacije. Pored toga, ova zajednička varijanta može da utiče na kog- nitivne funkcije, što je utvrdeno testom CPT-IP kod šizofrenih bolesnika.

journal of medical biochemistry

Common Variants in BCL9 Gene and Schizophrenia in a Japanese Population: Association Study, Meta-Analysis and Cognitive Function Analysis / UOBIČAJENE VARIJANTE BCL9 GENA I ŠIZOFRENIJA U JAPANSKOJ POPULACIJI: ŠTUDIJA POVEZANOSTI, METAANALIZA I ANALIZA KOGNITIVNIH FUNKCIJA