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.
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.
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Authors: H Kilpinen; T Ylisaukko-Oja; W Hennah; O M Palo; T Varilo; R Vanhala; T Nieminen-von Wendt; L von Wendt; T Paunio; L Peltonen Journal: Mol Psychiatry Date: 2007-06-19 Impact factor: 15.992
Authors: Weidong Li; Yu Zhou; J David Jentsch; Robert A M Brown; Xiaoli Tian; Dan Ehninger; William Hennah; Leena Peltonen; Jouko Lönnqvist; Matti O Huttunen; Jaakko Kaprio; Joshua T Trachtenberg; Alcino J Silva; Tyrone D Cannon Journal: Proc Natl Acad Sci U S A Date: 2007-11-02 Impact factor: 11.205
Authors: W Hennah; P Thomson; A McQuillin; N Bass; A Loukola; A Anjorin; D Blackwood; D Curtis; I J Deary; S E Harris; E T Isometsä; J Lawrence; J Lönnqvist; W Muir; A Palotie; T Partonen; T Paunio; E Pylkkö; M Robinson; P Soronen; K Suominen; J Suvisaari; S Thirumalai; D St Clair; H Gurling; L Peltonen; D Porteous Journal: Mol Psychiatry Date: 2008-03-04 Impact factor: 15.992
Authors: Steven J Clapcote; Tatiana V Lipina; J Kirsty Millar; Shaun Mackie; Sheila Christie; Fumiaki Ogawa; Jason P Lerch; Keith Trimble; Masashi Uchiyama; Yoshiyuki Sakuraba; Hideki Kaneda; Toshihiko Shiroishi; Miles D Houslay; R Mark Henkelman; John G Sled; Yoichi Gondo; David J Porteous; John C Roder Journal: Neuron Date: 2007-05-03 Impact factor: 17.173
Authors: A Raznahan; Y Lee; R Long; D Greenstein; L Clasen; A Addington; J L Rapoport; J N Giedd Journal: Mol Psychiatry Date: 2010-07-13 Impact factor: 15.992
Authors: Nicholas C Stefanis; Alex Hatzimanolis; Nikolaos Smyrnis; Dimitrios Avramopoulos; Ioannis Evdokimidis; Jim van Os; Costas N Stefanis; Richard E Straub; Daniel R Weinberger Journal: Schizophr Bull Date: 2011-11-24 Impact factor: 9.306