Search

Background Large sample sizes are often required to detect statistically significant associations between pharmacogenetic markers and treatment response. Meta-analysis may be performed to synthesize data from several studies, increasing sample size and, consequently, power to detect significant genetic effects. However, performing robust synthesis of data from pharmacogenetic studies is often challenging because of poor reporting of key data in study reports. There is currently no guideline for the reporting of pharmacogenetic studies that has been developed using a widely accepted robust methodology. The objective of this project was to develop the STrengthening the Reporting Of Pharmacogenetic Studies (STROPS) guideline. Methods and findings We established a preliminary checklist of reporting items to be considered for inclusion in the guideline. We invited representatives of key stakeholder groups to participate in a 2-round Delphi survey. A total of 52 individuals participated in both rounds of the survey, scoring items with regards to their importance for inclusion in the STROPS guideline. We then held a consensus meeting, at which 8 individuals considered the results of the Delphi survey and voted on whether each item ought to be included in the final guideline. The STROPS guideline consists of 54 items and is accompanied by an explanation and elaboration document. The guideline contains items that are particularly important in the field of pharmacogenetics, such as the drug regimen of interest and whether adherence to treatment was accounted for in the conducted analyses. The guideline also requires that outcomes be clearly defined and justified, because in pharmacogenetic studies, there may be a greater number of possible outcomes than in other types of study (for example, disease–gene association studies). A limitation of this project is that our consensus meeting involved a small number of individuals, the majority of whom are based in the United Kingdom. Conclusions Our aim is for the STROPS guideline to improve the transparency of reporting of pharmacogenetic studies and also to facilitate the conduct of high-quality systematic reviews and meta-analyses. We encourage authors to adhere to the STROPS guideline when publishing pharmacogenetic studies., Marty Chaplin and co-authors recount the development of a guideline for reporting pharmacogenetic studies.

Brain-derived neurotrophic factor (BDNF) has important roles in neural cell growth and differentiation. Despite multiple lines of evidence suggesting BDNF as a possible contributor to the pathogenesis of bipolar disorder (BD), the results of genetic association studies have been mixed. We hypothesize that BDNF gene polymorphisms may confer increased susceptibility to BD.Using a cohort of multiplex bipolar families, we performed family-based association testing to look for associations between BD and eight single nucleotide polymorphisms (SNPs) from BDNF.We found associations (p0.05) between BD and six of the eight SNPs analysed, including two SNPs not previously investigated in association studies. We were able to replicate associations previously found between BD and the Val66Met polymorphism of BDNF (rs6265) and the SNPs rs1519480 and rs12273363. We also found evidence of an association between rs11030107 and BD that was not found in a previous study.Our results support the hypothesis that some BDNF gene polymorphisms may be contributing factors in the pathogenesis of BD. Our study also adds to the body of evidence associating the functional Val66Met polymorphism of BDNF with BD.

In this report we describe a rapid polymerase chain reaction (PCR) based method for the detection of beta-thalassaemia (beta-thal) mutations. This method is based on the visualization of unique DNA heteroduplex banding patterns, following non-denaturing polyacrylamide gel electrophoresis, resulting from hybridization between mutant PCR products and synthetic DNA heteroduplex generator molecules. Using the Singaporean population, which consists of Chinese, Malay and Asian Indian ethnic groups, as a model, we have constructed and evaluated three DNA heteroduplex generator molecules for the detection of the common beta-thalassaemia mutations found in this population. The results show that these three molecules are capable of detecting approximately 95% of the mutations found in the Singaporean population. We propose that this technology may be applied as an alternative screening strategy for beta-thalassaemia mutations because it is technically simple, flexible, cost-effective, and requires only minimal laboratory resources.