Association of variants in DISC1 with psychosis-related traits in a large population cohort.
BACKGROUND
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.


METHODS
We examined 41 single-nucleotide polymorphisms within DISC1 and performed tests of association with 4 quantitative phenotypes.


METHODS
Academic research.


METHODS
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.


METHODS
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.
Tomppo
Liisa
L
Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland. Jesper.Ekelund@ktl.fi
Hennah
William
W
Miettunen
Jouko
J
Järvelin
Marjo-Riitta
MR
Veijola
Juha
J
Ripatti
Samuli
S
Lahermo
Päivi
P
Lichtermann
Dirk
D
Peltonen
Leena
L
Ekelund
Jesper
J
D000328:Adult; D000342:Affective Symptoms / Q000235:genetics; D000483:Alleles; D015331:Cohort Studies; D005260:Female; D005387:Finland; D005500:Follow-Up Studies; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000235:genetics* / Q000523:psychology; D012559:Schizophrenia / Q000235:genetics*; D012565:Schizophrenic Psychology; D012919:Social Behavior
C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins