Mutation screening of the Homer gene family and association analysis in schizophrenia.
Homer proteins are a group of proteins that regulate group 1 metabotropic glutamate receptor function. As altered glutamate function has been implicated in many neuro psychiatric disorders, particularly schizophrenia, we have screened all three known Homer genes for sequence variation for use under the candidate gene association paradigm. We found seven SNPs, including three in exons. Of these, none was non-synonymous. Allele frequencies of all the detected SNPs were estimated in DNA pools of 368 schizophrenics and 368 controls. Only one (Homer 1 IVS4 + 18A > G) was associated with schizophrenia in this sample, a finding confirmed by individual genotyping (P = 0.01). However, in our extended sample of 680 cases and 671 controls, the evidence for association diminished (P = 0.05). Our results suggest it is unlikely that sequence variants in the Homer genes contribute to the aetiology of schizophrenia, but the variants we identified are plausible candidates for other neuropsychiatric phenotypes.
Norton
N
N
Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, United Kingdom.
Williams
H J
HJ
Williams
N M
NM
Spurlock
G
G
Zammit
S
S
Jones
G
G
Jones
S
S
Owen
R
R
O'Donovan
M C
MC
Owen
M J
MJ
D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D005838:Genotype; D000072233:Homer Scaffolding Proteins; D006801:Humans; D007494:Ireland; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics*; D009479:Neuropeptides / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D006113:United Kingdom
D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D009479:Neuropeptides