Abstract
Autism is a common, severe and highly heritable neurodevelopmental disorder. The International Molecular Genetic Study of Autism Consortium (IMGSAC) genome screen for linkage in affected sib-pair families identified a chromosome 7q susceptibility locus (AUTS1), that has subsequently shown evidence of increased sharing in several independent multiplex samples and in two meta-analyses. Taking into account the location of the MET gene under this linkage peak, and the fact that it has recently been reported to be associated with autism, the gene was further analyzed as a promising autism candidate. The gene encodes a transmembrane receptor tyrosine kinase of the hepatocyte growth factor/ scatter factor (HGF/SF). MET is best known as an oncogene, but its signalling also participates in immune function, peripheral organ development and repair, and the development of the cerebral cortex and cerebellum (all of which have been observed earlier as being disregulated in individuals with autism). Here we present a family-based association analysis covering the entire MET locus. Significant results were obtained in both single locus and haplotype approaches with a single nucleotide polymorphism in intron 1 (rs38845, P <0.004) and with one intronic haplotype (AAGTG, P <0.009) in 325 multiplex IMGSAC families and 10 IMGSAC trios. Although these results failed to replicate in an independent sample of 82 Italian trios, the association itself was confirmed by a case-control analysis performed using the Italian cohort (P <0.02). The previously reported positive association of rs1858830 failed to replicate in this study. Overall, our findings provide further evidence that MET may play a role in autism susceptibility.
| Original language | English |
|---|---|
| Pages (from-to) | 749-758 |
| Number of pages | 10 |
| Journal | European Journal of Human Genetics |
| Volume | 17 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2009 |
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ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
Cite this
MET and autism susceptibility : Family and case-control studies. / Sousa, Inês; Clark, Taane G.; Toma, Claudio; Kobayashi, Kazuhiro; Choma, Maja; Holt, Richard; Sykes, Nuala H.; Lamb, Janine A.; Bailey, Anthony J.; Battaglia, Agatino; Maestrini, Elena; Monaco, Anthony P.
In: European Journal of Human Genetics, Vol. 17, No. 6, 2009, p. 749-758.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MET and autism susceptibility
T2 - Family and case-control studies
AU - Sousa, Inês
AU - Clark, Taane G.
AU - Toma, Claudio
AU - Kobayashi, Kazuhiro
AU - Choma, Maja
AU - Holt, Richard
AU - Sykes, Nuala H.
AU - Lamb, Janine A.
AU - Bailey, Anthony J.
AU - Battaglia, Agatino
AU - Maestrini, Elena
AU - Monaco, Anthony P.
PY - 2009
Y1 - 2009
N2 - Autism is a common, severe and highly heritable neurodevelopmental disorder. The International Molecular Genetic Study of Autism Consortium (IMGSAC) genome screen for linkage in affected sib-pair families identified a chromosome 7q susceptibility locus (AUTS1), that has subsequently shown evidence of increased sharing in several independent multiplex samples and in two meta-analyses. Taking into account the location of the MET gene under this linkage peak, and the fact that it has recently been reported to be associated with autism, the gene was further analyzed as a promising autism candidate. The gene encodes a transmembrane receptor tyrosine kinase of the hepatocyte growth factor/ scatter factor (HGF/SF). MET is best known as an oncogene, but its signalling also participates in immune function, peripheral organ development and repair, and the development of the cerebral cortex and cerebellum (all of which have been observed earlier as being disregulated in individuals with autism). Here we present a family-based association analysis covering the entire MET locus. Significant results were obtained in both single locus and haplotype approaches with a single nucleotide polymorphism in intron 1 (rs38845, P <0.004) and with one intronic haplotype (AAGTG, P <0.009) in 325 multiplex IMGSAC families and 10 IMGSAC trios. Although these results failed to replicate in an independent sample of 82 Italian trios, the association itself was confirmed by a case-control analysis performed using the Italian cohort (P <0.02). The previously reported positive association of rs1858830 failed to replicate in this study. Overall, our findings provide further evidence that MET may play a role in autism susceptibility.
AB - Autism is a common, severe and highly heritable neurodevelopmental disorder. The International Molecular Genetic Study of Autism Consortium (IMGSAC) genome screen for linkage in affected sib-pair families identified a chromosome 7q susceptibility locus (AUTS1), that has subsequently shown evidence of increased sharing in several independent multiplex samples and in two meta-analyses. Taking into account the location of the MET gene under this linkage peak, and the fact that it has recently been reported to be associated with autism, the gene was further analyzed as a promising autism candidate. The gene encodes a transmembrane receptor tyrosine kinase of the hepatocyte growth factor/ scatter factor (HGF/SF). MET is best known as an oncogene, but its signalling also participates in immune function, peripheral organ development and repair, and the development of the cerebral cortex and cerebellum (all of which have been observed earlier as being disregulated in individuals with autism). Here we present a family-based association analysis covering the entire MET locus. Significant results were obtained in both single locus and haplotype approaches with a single nucleotide polymorphism in intron 1 (rs38845, P <0.004) and with one intronic haplotype (AAGTG, P <0.009) in 325 multiplex IMGSAC families and 10 IMGSAC trios. Although these results failed to replicate in an independent sample of 82 Italian trios, the association itself was confirmed by a case-control analysis performed using the Italian cohort (P <0.02). The previously reported positive association of rs1858830 failed to replicate in this study. Overall, our findings provide further evidence that MET may play a role in autism susceptibility.
UR - http://www.scopus.com/inward/record.url?scp=67349232519&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67349232519&partnerID=8YFLogxK
U2 - 10.1038/ejhg.2008.215
DO - 10.1038/ejhg.2008.215
M3 - Article
C2 - 19002214
AN - SCOPUS:67349232519
VL - 17
SP - 749
EP - 758
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 6
ER -