DOCK4 and CEACAM21 as novel schizophrenia candidate genes in the Jewish population

Anna Alkelai, Sara Lupoli, Lior Greenbaum, Yoav Kohn, Kyra Kanyas-Sarner, Edna Ben-Asher, Doron Lancet, Fabio MacCiardi, Bernard Lerer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

It is well accepted that schizophrenia has a strong genetic component. Several genome-wide association studies (GWASs) of schizophrenia have been published in recent years; most of them population based with a case-control design. Nevertheless, identifying the specific genetic variants which contribute to susceptibility to the disorder remains a challenging task. A family-based GWAS strategy may be helpful in the identification of schizophrenia susceptibility genes since it is protected against population stratification, enables better accounting for genotyping errors and is more sensitive for identification of rare variants which have a very low frequency in the general population. In this project we implemented a family-based GWAS of schizophrenia in a sample of 107 Jewish-Israeli families. We found one genome-wide significant association in the intron of the DOCK4 gene (rs2074127, p value=1.13410 7) and six additional nominally significant association signals with p<1105. One of the top single nucleotide polymorphisms (p<1105) which is located in the predicted intron of the CEACAM21 gene was significantly replicated in independent family-based sample of Arab-Israeli origin (rs4803480: p value=0.002; combined p value=9.6110 8), surviving correction for multiple testing. Both DOCK4 and CEACAM21 are biologically reasonable candidate genes for schizophrenia although generalizability of the association of DOCK4 with schizophrenia should be investigated in further studies. In addition, gene-wide significant associations were found within three schizophrenia candidate genes: PGBD1, RELN and PRODH, replicating previously reported associations. By application of a family-based strategy to GWAS, our study revealed new schizophrenia susceptibility loci in the Jewish-Israeli population.

Original languageEnglish
Pages (from-to)459-469
Number of pages11
JournalInternational Journal of Neuropsychopharmacology
Volume15
Issue number4
DOIs
StatePublished - May 2012
Externally publishedYes

Funding

FundersFunder number
Seventh Framework Programme216088

    Keywords

    • CEACAM21
    • DOCK4
    • GWAS
    • genes
    • schizophrenia

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