ZDHHC8 as a candidate gene for schizophrenia: analysis of a putative functional intronic marker in case-control and family-based association studies.
BACKGROUND
The chromosome 22q11 region is proposed as a major candidate locus for susceptibility genes to schizophrenia. Recently, the gene ZDHHC8 encoding a putative palmitoyltransferase at 22q11 was proposed to increase liability to schizophrenia based on both animal models and human association studies by significant over-transmission of allele rs175174A in female, but not male subjects with schizophrenia.


METHODS
Given the genetic complexity of schizophrenia and the potential genetic heterogeneity in different populations, we examined rs175174 in 204 German proband-parent triads and in an independent case-control study (schizophrenic cases: n = 433; controls: n = 186).


RESULTS
In the triads heterozygous parents transmitted allele G preferentially to females, and allele A to males (heterogeneity chi2 = 4.43; p = 0.035). The case-control sample provided no further evidence for overall or gender-specific effects regarding allele and genotype frequency distributions.


CONCLUSIONS
The findings on rs175174 at ZDHHC8 are still far from being conclusive, but evidence for sexual dimorphism is moderate, and our data do not support a significant genetic contribution of rs175174 to the aetiopathogenesis of schizophrenia.
Faul
Thomas
T
Department of Psychiatry and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany. thomas.faul@gmx.de
Gawlik
Micha
M
Bauer
Martin
M
Jung
Sven
S
Pfuhlmann
Bruno
B
Jabs
Burkhard
B
Knapp
Michael
M
Stöber
Gerald
G
D000217:Acyltransferases / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D005190:Family; D005260:Female; D018740:Genetic Heterogeneity; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D012727:Sex Characteristics; D012737:Sex Factors; D016335:Zinc Fingers / Q000235:genetics*
D005819:Genetic Markers; D008565:Membrane Proteins; D000217:Acyltransferases; C488097:ZDHHC8 protein, human