Original ArticleAKT1 Is Associated with Schizophrenia Across Multiple Symptom Dimensions in the Irish Study of High Density Schizophrenia Families
Section snippets
Subjects and Phenotypes
The ISHDSF sample comprises 265 high-density schizophrenia families with 1408 individuals available for genotyping (22). All participating individuals gave appropriate informed consent to the study. The sample was divided into four concentric diagnostic categories for analysis purposes, ranging from narrow to very broad spectrum disease. Briefly, D2 (core schizophrenia) includes schizophrenia, poor-outcome schizoaffective disorder, and simple schizophrenia; D5 (narrow psychosis spectrum)
Results
Table 1 lists the AKT1 SNP locations and allele frequencies in the ISHDSF, which are similar to those of Emamian et al. (6). AKT1 has 14–15 known exons (depending on splice variant) spanning approximately 24.2 kilobases (kb) (Figure 1). Genotype frequencies of all SNPs were in HWE (data not shown).
Discussion
As is increasingly observed in complex disease association studies, reports on AKT1 and schizophrenia reveal inconsistent replication of a particular allele combination, yet replication at a broader level, i.e. the SNP or haplotype and ultimately the gene itself (43, 44). Potential reasons for such diverse findings are sample size, heterogenous phenotypes, marker sets, allele frequencies or LD structure, genetic admixture, multiple testing issues, and indeed true heterogeneity in variants that
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