CCDC68 and Schizophrenia

Recent genome‑wide association studies have implicated CCDC68 in schizophrenia by identifying non‑coding common risk alleles. In one study, a variant, rs4309482[A] located between CCDC68 and TCF4, reached genome‑wide significance (OR = 1.09, P = 7.8 × 10(-9)) in an analysis including 7,946 cases (PMID:21791550), and a second study reported consistent statistical support in a cohort of 173 patients (PMID:24160291). Despite the large sample sizes, these associations are based solely on statistical findings without additional familial segregation or functional validation in the context of schizophrenia. The genetic evidence is therefore derived from population‐based risk estimates rather than Mendelian segregation, limiting the current clinical validity of CCDC68 as a standalone diagnostic marker.

Functional studies of CCDC68 have primarily focused on a tumor‑suppressive role in pancreatic ductal adenocarcinoma (PMID:25381825) and do not provide direct support for its mechanistic involvement in schizophrenia. Although the statistical associations are robust, the lack of confirmatory functional evidence or clear segregation data in schizophrenia patients constrains the gene‑disease validity to a limited level. Key take‑home: While CCDC68 may modestly contribute to schizophrenia risk, further functional and segregation studies are essential before incorporating it into routine clinical diagnostic or commercial testing workflows.

References

• Human Molecular Genetics • 2011 • Common variants at VRK2 and TCF4 conferring risk of schizophrenia PMID:21791550
• Behavioral and Brain Functions • 2013 • The impact of the genome‑wide supported variant in the cyclin M2 gene on gray matter morphology in schizophrenia PMID:24160291
• Oncogene • 2015 • Coiled‑coil domain containing 68 (CCDC68) demonstrates a tumor‑suppressive role in pancreatic ductal adenocarcinoma PMID:25381825

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