Genome-Wide Gene-Environment Interaction Analysis Using Set-Based Association Tests

The past year has witnessed substantial advances in understanding the genetic basis of many common phenotypes of biomedical importance. These advances have been the result of systematic, well-powered, genome-wide surveys exploring the relationships between common sequence variation and disease predisposition. This approach has revealed over 50 disease-susceptibility loci and has provided insights into the allelic architecture of multifactorial traits. At the same time, much has been learned about the successful prosecution of association studies on such a scale. This Review highlights the knowledge gained, defines areas of emerging consensus, and describes the challenges that remain as researchers seek to obtain more complete descriptions of the susceptibility architecture of biomedical traits of interest and to translate the information gathered into improvements in clinical management.

Background Hypertension, being the root cause of many of the body sytem and organs failure, remains to be a major public health challenge globally. Though the problem is huge in both developed and developing countries, data are scarce in developing countries like Ethiopia. Therefore, this study was aimed to determine the magnitude and associated factors of hypertension in North West Ethiopia. Methods A cross-sectional survey was conducted on adults aged 35 years and above in the rural and urban communities of Dabat district and Gondar town in 2012. The data were collected using the WHO STEPwise strategy. Hypertension was defined as having a Systolic blood pressure of ≥140 mmHg and/ or a Diastolic BP of ≥ 90mmHg or a reported use of anti-hypertensive medications for raised blood pressure. Prevalence was computed with a 95% confidence interval. Selected risk factors were assessed using a biviarete logistic regression. Results A total of 2200 participants were included in the study. The median age (±SD) was 47 (±12.4) years. The overall prevalence of hypertension was found to be 27.9% [95% CI 26.0, 29.8], with the proportion in the urban and rural residents being 30.7% and 25.3% respectively. The prevalence of hypertension was 29.3% for women and 26.3% for men. Out of the 598 hypertensive patients 241 (40.3%) had blood pressure measurements, and 99 (16.6%) had known hypertension and were on treatment. The proportion of systolic and diastolic hypertension in this subgroup of adults was 133(6.2%). The multivariable logistic regression analysis showed older age (AOR = 1.06; 1.05, 1.07), raised fasting glucose (AOR = 1.01; 1.001, 1.01), alcohol consumption (AOR = 1.71; 1.24, 2.36), and raised BMI (AOR =1.07; 1.04, 1.10) were significantly associated with hypertension. Conclusion The prevalence of hypertension was considerably higher in rural areas than previously reported. The health system needs to develop strategies to increase the reach of relevant screening and diagnostic services to both rural and urban populations.

Objective To evaluate the use of prospective screening for the HLA-B*58:01 allele to identify Taiwanese individuals at risk of severe cutaneous adverse reactions (SCARs) induced by allopurinol treatment. Design National prospective cohort study. Setting 15 medical centres in different regions of Taiwan, from July 2009 to August 2014. Participants 2926 people who had an indication for allopurinol treatment but had not taken allopurinol previously. Participants were excluded if they had undergone a bone marrow transplant, were not of Han Chinese descent, and had a history of allopurinol induced hypersensitivity. DNA purified from 2910 participants’ peripheral blood was used to assess the presence of HLA-B*58:01. Main outcome measures Incidence of allopurinol induced SCARs with and without screening. Results Participants who tested positive for HLA-B*58:01 (19.6%, n=571) were advised to avoid allopurinol, and were referred to an alternate drug treatment or advised to continue with their prestudy treatment. Participants who tested negative (80.4%, n=2339) were given allopurinol. Participants were interviewed once a week for two months to monitor symptoms. The historical incidence of allopurinol induced SCARs, estimated by the National Health Insurance research database of Taiwan, was used for comparison. Mild, transient rash without blisters developed in 97 (3%) participants during follow-up. None of the participants was admitted to hospital owing to adverse drug reactions. SCARs did not develop in any of the participants receiving allopurinol who screened negative for HLA-B*58:01. By contrast, seven cases of SCARs were expected, based on the estimated historical incidence of allopurinol induced SCARs nationwide (0.30% per year, 95% confidence interval 0.28% to 0.31%; P=0.0026; two side one sample binomial test). Conclusions Prospective screening of the HLA-B*58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres.