Evaluation Of Polygenic Risk Score For Schizophrenia Among Northern Finland Birth Cohort 1966 Data

• Main Author: Miettunen, Jouko
• Format: Other/Unknown Material
• Language: English
• Published: Morressier 2017
• Subjects: Meier; Northern Finland
• Online Access: https://openresearchlibrary.org/viewer/579ed52a-2115-409b-a8d4-cc43dc5ccef2; https://openresearchlibrary.org/ext/api/media/579ed52a-2115-409b-a8d4-cc43dc5ccef2/assets/external_content.pdf; https://doi.org/10.26226/morressier.5c642bee9ae8fb00131cfb79

IntroductionPsychotic disorders, such as schizophrenia, are severe mental disorders that affect about 3% of the Finnish population. In Northern Finland, the percentage is even higher (4.5%). Generally, the heritability among psychotic disorders is considered high even though most of the children of parents with psychotic disorder remain without psychotic diagnosis. Using polygenic risk score (PRS) for schizophrenia (SCH), it is possible to estimate personal genetic risk and try to evaluate why only some of the children of parents with psychotic disorder develop psychotic disorder themselves.ObjectivesTo calculate PRS for schizophrenia and evaluate it among Northern Finland Birth Cohort 1966 (NFBC1966) data.MethodsThe NFBC1966 is a large longitudinal and still ongoing birth cohort which consists of more than 12 000 cohort members born in 1966 in the Northern Finland. The calculation of PRS is based on previous results of genome-wide association studies on schizophrenia. Information on psychotic disorders is based on nationwide registers (Care Register for Health Care and the registers from Social Insurance Institution and Finnish Center for Pensions).Cox regression analysis (Hazard Ratios, HR) was used to estimate association between PRS and psychotic disorder. Kaplan-Meier survival analysis (Mantel-Cox estimate) was used to estimate the incidence of psychotic disorders.Previously found risk factors (gender, obstetric complications, maternal antenatal depression, unwantedness of a pregnancy, grand multiparity and childu2019s viral central nervous system infection) for psychotic disorders were used as covariates.ResultsGenetic data was available from 5 363 (48.2% male; 51.8% female) subjects. From them, 3.7% (N=196) was diagnosed with a psychotic disorder. When PRS increased, the risk (adjusted HR) for psychotic disorder was 1.30-fold (95% confidence interval=1.13-1.50, p=0.001). Similar results were found when different psychoses were evaluated separately. Those who had higher than the mean PRS were diagnosed with psychotic disorder more previously and frequently than the others (Mantel-Cox estimate: u03c72=10.4. df=1, p=0.001). Again, similar results occurred while observing different psychoses separately.ConclusionsPRS for schizophrenia is a sufficient estimate of personal genetic risk for a psychotic disorder among NFBC1966. People with higher PRS were diagnosed more often and earlier with psychotic disorder than people with lower PRS.