Association Study of 167 Candidate Genes for Schizophrenia Selected by a Multi-Domain Evidence-Based Prioritization Algorithm and Neurodevelopmental Hypothesis

Integrating evidence from multiple domains is useful in prioritizing disease candidate genes for subsequent testing. We ranked all known human genes (n = 3819) under linkage peaks in the Irish Study of High-Density Schizophrenia Families using three different evidence domains: 1) a meta-analysis of microarray gene expression results using the Stanley Brain collection, 2) a schizophrenia protein-protein interaction network, and 3) a systematic literature search. Each gene was assigned a domain-specific p-value and ranked after evaluating the evidence within each domain. For comparison to this
ranking process, a large-scale candidate gene hypothesis was also tested by including genes with Gene Ontology terms related to neurodevelopment. Subsequently, genotypes of 3725 SNPs in 167 genes from a custom Illumina iSelect array were used to evaluate the top ranked vs. hypothesis selected genes. Seventy-three genes were both highly ranked and involved in neurodevelopment (category 1) while 42 and 52 genes were exclusive to neurodevelopment (category 2) or highly ranked (category 3), respectively. The most significant associations were observed in genes PRKG1, PRKCE, and CNTN4 but no individual SNPs were significant after correction for multiple testing. Comparison of the approaches showed an excess of significant tests using the hypothesis-driven neurodevelopment category. Random selection of similar sized genes from two independent genome-wide association studies (GWAS) of schizophrenia showed the excess was unlikely by chance. In a further meta-analysis of three GWAS datasets, four candidate SNPs reached nominal significance. Although gene ranking using integrated sources of prior information did not enrich for significant results in the current experiment, gene selection using an a priori hypothesis (neurodevelopment) was superior to random selection. As such, further development of gene ranking strategies using more carefully selected sources of information is warranted.

A J-band detection of the sub-stellar mass donor in SDSS J1433+1011

We present time-resolved J-band spectroscopy of the short-period cataclysmic variable SDSS J143317.78+101123.3. We detect absorption lines from the sub-stellar donor star in this system, which contributes 38 +/- 5 per cent to the J-band light. From the relative strengths of the absorption lines in the J band, we estimate the spectral type of the donor star to be L2 +/- 1. These data are the first spectroscopic detection of a donor with a confirmed sub-stellar mass in a cataclysmic variable, and the spectral type is consistent with that expected from semi-empirical evolutionary models.

Using skew mapping, we have been able to derive an estimate for the radial velocity of the donor of K-d = 520 +/- 60 km/s. This value is consistent with, though much less precise than, predictions from mass determinations found via photometric fitting of the eclipse light curves.