Elevated risk of invasive group A streptococcal disease and host genetic variation in the human leucocyte antigen locus.
29 August 2019
Parks T, Elliott K, Lamagni T, Auckland K, Mentzer AJ, Guy R, Cartledge D, Strakova L, Connor DO, Pollard AJ, Neville MJ, Mahajan A, Ashrafian H, Chapman SJ, Hill AVS, Sriskandan S, Knight JC.
Genes and Immunity, (2019) pg 63–70
Invasive group A streptococcal (GAS) disease is uncommon but carries a high case-fatality rate relative to other infectious diseases. Given the ubiquity of mild GAS infections, it remains unclear why healthy individuals will occasionally develop life-threatening infections, raising the possibility of host genetic predisposition. Here, we present the results of a case–control study including 43 invasive GAS cases and 1540 controls. Using HLA imputation and linear mixed models, we find each copy of the HLA-DQA1*01:03 allele associates with a twofold increased risk of disease (odds ratio 2.3, 95% confidence interval 1.3–4.4, P = 0.009), an association which persists with classical HLA typing of a subset of cases and analysis with an alternative large control dataset with validated HLA data. Moreover, we propose the association is driven by the allele itself rather than the background haplotype. Overall this finding provides impetus for further investigation of the immunogenetic basis of this devastating bacterial disease.
A Multi-tissue Transcriptome Analysis of Human Metabolites Guides Interpretability of Associations Based on Multi-SNP Models for Gene Expression.
23 January 2020
Ndungu A, Payne A, Torres JM, van de Bunt M, McCarthy MI. American Journal of Human Genetics, (2020) pg 188-201 Abstract There is particular interest in transcriptome-wide association studies...
Association between beta-blocker use and mortality/morbidity in older patients with heart failure with reduced ejection fraction. A propensity score-matched analysis from the Swedish Heart Failure Registry.
3 September 2019
Stolfo D, Uijl A, Benson L, Schrage B, Fudim M, Asselbergs FW, Koudstaal S, Sinagra G, Dahlstram U, Rosano G, Savarese G. European Journal of Heart Failure, (2019) pg...