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Association of Variants in DISC1 With Psychosis-Related Traits in a Large Population Cohort
Liisa Tomppo, BM;
William Hennah, PhD;
Jouko Miettunen, PhD;
Marjo-Riitta Järvelin, MD, PhD;
Juha Veijola, MD, PhD;
Samuli Ripatti, PhD;
Päivi Lahermo, PhD;
Dirk Lichtermann, MD, PhD;
Leena Peltonen, MD, PhD;
Jesper Ekelund, MD, PhD
Arch Gen Psychiatry. 2009;66(2):134-141.
Context There is an abundance of data from human genetic studies and animal models that implies a role for the disrupted in schizophrenia 1 gene (DISC1) in the etiology of schizophrenia and other major mental illnesses.
Objective To study the effect of previously identified risk alleles of DISC1 on quantitative intermediate phenotypes for psychosis in an unselected population.
Design We examined 41 single-nucleotide polymorphisms within DISC1 and performed tests of association with 4 quantitative phenotypes.
Setting Academic research.
Participants Individuals from an unselected birth cohort in Finland. Originally, everyone born in the catchment area in 1966 (N = 12 058) was included in the study. Of these, 4651 (38.6%) attended the 31-year follow-up and could be included in the study.
Main Outcome Measures Scores on 4 psychometric instruments selected to function as proxies for positive and negative aspects of psychotic disorders, including the Perceptual Aberration Scale, Revised Social Anhedonia Scale, Revised Physical Anhedonia Scale, and Schizoidia Scale by Golden and Meehl.
Results Carriers of the minor allele of marker rs821577 had significantly higher scores on social anhedonia (P < .001). The minor allele of marker rs821633 was strongly associated with lower scores on social anhedonia when analyzed dependent on the absence of the minor alleles of markers rs1538979 and rs821577 (P < .001).
Conclusions Variants in DISC1 affect the level of social anhedonia, a cardinal symptom of schizophrenia in the general population. DISC1 might be more central to human psychological functioning than previously thought, as it seems to affect the degree to which people enjoy social interactions.
Author Affiliations: Departments of Molecular Medicine (Ms Tomppo and Drs Hennah, Ripatti, Lichtermann, Peltonen, and Ekelund) and Mental Health and Alcohol Research (Dr Ekelund), National Public Health Institute, and Department of Psychiatry (Dr Ekelund) and Finnish Genome Center (Dr Lahermo), University of Helsinki, Helsinki, and Departments of Psychiatry (Drs Miettunen and Veijola) and Public Health Science and General Practice (Dr Järvelin), University of Oulu, Oulu, Finland; Medical Genetics Section, University of Edinburgh, Edinburgh (Dr Hennah), Division of Epidemiology, Public Health and Primary Care, Imperial College, London (Dr Järvelin), and Human Genetics Section, Wellcome Trust Sanger Institute, Cambridge (Dr Peltonen), United Kingdom; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden (Dr Ripatti); and Café Ersatz, Bonn, Germany (Dr Lichtermann).
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