IGF1, growth pathway polymorphisms and schizophrenia: a pooling study.
It has been hypothesized that insulin-like growth factors (IGFs) and components of the growth-hormone (GH)-IGF axis may underlie reported associations of poor fetal and childhood growth with schizophrenia. We have investigated the association of schizophrenia with 16 SNPs spanning the IGF1 gene with an inter-marker distance of approximately 2-3 kb. We also examined associations with four common functional polymorphisms of genes involved in aspects of the GH-IGF system--the IGF1 receptor (IGF1R), insulin receptor substrate (IRS1), growth hormone (GH1), and IGF binding protein-3 (IGFBP3). The study was based on an analysis of pooled DNA samples from 648 UK and Irish cases of schizophrenia and 712 blood donor controls and of 297 Bulgarian parent offspring trios. In replicated pool analyses, none of the 16 SNPs in IGF1 nor the 4 key SNPs in the other growth pathway genes were associated with schizophrenia. SNP coverage of IGF1 was extensive, so our findings do not support a major role for IGF-I in the aetiology of schizophrenia.
Gunnell
D
D
Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol, UK. D.J.Gunnell@Bristol.ac.uk
Lewis
S
S
Wilkinson
J
J
Georgieva
L
L
Davey
G Smith
GS
Day
I N M
IN
Holly
J M P
JM
O'Donovan
M C
MC
Owen
M J
MJ
Kirov
G
G
Zammit
S
S
D002031:Bulgaria; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D005260:Female; D019382:Human Growth Hormone / Q000235:genetics; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D007494:Ireland; D015810:Linkage Disequilibrium; D008297:Male; D010750:Phosphoproteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D006113:United Kingdom
C515497:IGFBP3 protein, human; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D010750:Phosphoproteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D004247:DNA