ABSTRACT
Aims: In single-nucleotide polymorphism (SNP) scans, SNP-phenotype association hypotheses are tested, however there is biological interpretation only for genes that span multiple SNPs. We demonstrate and validate a method of combining gene-wide evidence using data for high-density lipoprotein cholesterol (HDLC). Methodology: In a family based study (N=1782 from 482 families), we used 1000 phenotype-permuted datasets to determine the correlation of z-test statistics for 592 SNPHDLC association tests comprising 14 genes previously reported to be associated with HDLC. We generated gene-wide p-values using the distribution of the sum of correlated zstatistics. Results: Of the 14 genes, CETP was significant (p=4.0×10-5 <0.05/14), while PLTP was significant at the borderline (p=6.7×10-3 <0.1/14). These p-values were confirmed using empirical distributions of the sum of χ2 association statistics as a gold standard (2.9×10-6 and 1.8×10-3, respectively). Genewide p-values were more significant than Bonferronicorrected p-value for the most significant SNP in 11 of 14 genes (p=0.023). Genewide p- values calculated from SNP correlations derived for 20 simulated normally distributed phenotypes reproduced those derived from the 1000 phenotype-permuted datasets were correlated with the empirical distributions (Spearman correlation = 0.92 for both). Conclusion: We have validated a simple scalable method to combine polymorphism-level evidence into gene-wide statistical evidence. High-throughput gene-wide hypothesis tests may be used in biologically interpretable genomewide association scans. Genewide association tests may be used to meaningfully replicate findings in populations with different linkage disequilibrium structure, when SNP-level replication is not expected.
ABSTRACT
Objective: The slow discharge of long-term psychiatry patients from Weskoppies Hospital into the community has not matched the national and international drive towards deinstitutionalisation. This article investigates patient and social work factors related to successful community placement; in the context of limited community care facilities. Method: Thirty-six long-term patients who were successfully placed outside of the hospital during a seven month period were compared to 235 unplaced long-term patients in terms of demographic and clinical variables. Social work services were analysed in terms of which patients received the most interventions; and the most common type of interventions. Results: The most significant patient factors associated with successful placement were: female patients; medium-to-high level of functioning; having involved relatives living far away; a low frequency of behavioural problems (especially of cannabis abuse; verbal or physical aggression; uncontrolled sexual activity); and agitation or restlessness. These patient factors were mirrored in the social work services rendered to the long-term patients during the study period: The recipients were mostly female; in open wards (higher-functioning); and the social services utilised were mostly related to planning for placement and patient support. Conclusion: The lack of community care facilities in the Pretoria area that are able to care for the more difficult long-term psychiatry patients; limits successful placement and increases the burden of hospital based social workers. The problem cannot be resolved at a hospital level and needs to be addressed in the context of provincial and national health departments