Fine mapping of AHI1 as a schizophrenia susceptibility gene: from association to evolutionary evidence.

Details

Serval ID
serval:BIB_BBFEE310C2C7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Fine mapping of AHI1 as a schizophrenia susceptibility gene: from association to evolutionary evidence.
Journal
Faseb Journal : Official Publication of the Federation of American Societies For Experimental Biology
Author(s)
Torri F., Akelai A., Lupoli S., Sironi M., Amann-Zalcenstein D., Fumagalli M., Dal Fiume C., Ben-Asher E., Kanyas K., Cagliani R., Cozzi P., Trombetti G., Lievers L.S., Salvi E., Orro A., Beckmann J.S., Lancet D., Kohn Y., Milanesi L., Ebstein R.B., Lerer B., Macciardi F.
ISSN
0892-6638 (Print)
1530-6860 ([electronic])
0892-6638 ([linking])
Publication state
Published
Issued date
2010
Volume
24
Number
8
Pages
3066-82
Language
english
Notes
Publication types: JOURNAL ARTICLE
Publication Status: aheadofprint
Abstract
In previous studies, we identified a locus for schizophrenia on 6q23.3 and proposed the Abelson helper integration site 1 (AHI1) as the candidate gene. AHI1 is expressed in the brain and plays a key role in neurodevelopment, is involved in Joubert syndrome, and has been recently associated with autism. The neurodevelopmental role of AHI1 fits with etiological hypotheses of schizophrenia. To definitively confirm our hypothesis, we searched for associations using a dense map of the region. Our strongest findings lay within the AHI1 gene: single-nucleotide polymorphisms rs11154801 and rs7759971 showed significant associations (P=6.23E-06; P=0.84E-06) and haplotypes gave P values in the 10E-8 to 10E-10 range. The second highest significant region maps close to AHI1 and includes the intergenic region between BC040979 and PDE7B (rs2038549 at P=9.70E-06 and rs1475069 at P=6.97E-06), and PDE7B and MAP7. Using a sample of Palestinian Arab families to confirm these findings, we found isolated signals. While these results did not retain their significance after correction for multiple testing, the joint analysis across the 2 samples supports the role of AHI1, despite the presence of heterogeneity. Given the hypothesis of positive selection of schizophrenia genes, we resequenced a 11 kb region within AHI1 in ethnically defined populations and found evidence for a selective sweep. Network analysis indicates 2 haplotype clades, with schizophrenia-susceptibility haplotypes clustering within the major clade. In conclusion, our data support the role of AHI1 as a susceptibility gene for schizophrenia and confirm it has been subjected to positive selection, also shedding light on new possible candidate genes, MAP7 and PDE7B.-Torri, F., Akelai, A., Lupoli, S., Sironi, M., Amann-Zalcenstein, D., Fumagalli, M., Dal Fiume, C., Ben-Asher, E., Kanyas, K., Cagliani, R., Cozzi, P., Trombetti, G., Lievers, L. S., Salvi, E., Orro, A., Beckmann, J. S., Lancet, D., Kohn, Y., Milanesi, L., Ebstein, R. B., Lerer, B., Macciardi, F. Fine mapping of AHI1 as a schizophrenia susceptibility gene: from association to evolutionary evidence.
Keywords
AHI1, schizophrenia
Pubmed
Create date
12/05/2010 16:44
Last modification date
20/01/2021 6:26
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