Hemerich D, Pei J, Harakalova M, van Setten J, Boymans S, Boukens BJ, Efimov IR, Michels M, van der Velden J, Vink A, Cheng C, van der Harst P, Moore JH, Mokry M, Tragante V, Asselbergs FW.
Genomic and Precision Medicine, (2019) Vol 12 Issue 2
Regulatory elements may be involved in the mechanisms by which 52 loci influence myocardial mass, reflected by abnormal amplitude and duration of the QRS complex on the ECG. Functional annotation thus far did not take into account how these elements are affected in disease context.
We generated maps of regulatory elements on hypertrophic cardiomyopathy patients (ChIP-seq N=14 and RNA-seq N=11) and nondiseased hearts (ChIP-seq N=4 and RNA-seq N=11). We tested enrichment of QRS-associated loci on elements differentially acetylated and directly regulating differentially expressed genes between hypertrophic cardiomyopathy patients and controls. We further performed functional annotation on QRS-associated loci using these maps of differentially active regulatory elements.
Regions differentially affected in disease showed a stronger enrichment (P=8.6×10−5) for QRS-associated variants than those not showing differential activity (P=0.01). Promoters of genes differentially regulated between hypertrophic cardiomyopathy patients and controls showed more enrichment (P=0.001) than differentially acetylated enhancers (P=0.8) and super-enhancers (P=0.025). We also identified 74 potential causal variants overlapping these differential regulatory elements. Eighteen of the genes mapped confirmed previous findings, now also pinpointing the potentially affected regulatory elements and candidate causal variants. Fourteen new genes were also mapped.
Our results suggest differentially active regulatory elements between hypertrophic cardiomyopathy patients and controls can offer more insights into the mechanisms of QRS-associated loci than elements not affected by disease.
A pathology benchmarking tool to improve patient care by giving GPs simple, actionable insights
16 April 2019
OpenPathology is a new project being built by the EBM DataLab at the University of Oxford, supported by HDR UK. This repo is the code related to the website at https://openpathology.net. The code...
A validated natural language processing algorithm for brain imaging phenotypes from radiology reports in UK electronic health records
9 September 2019
Wheater E, Mair G, Sudlow C, Alex B, Grover C, Whiteley W. BMC Medical Informatics and Decision Making (2019) 19:184 BACKGROUND Manual coding of phenotypes in brain radiology reports is time...
Antimicrobial-impregnated central venous catheters for prevention of neonatal bloodstream infection (PREVAIL): an open-label, parallel-group, pragmatic, randomised controlled trial
1 June 2019
Gilbert R, Brown M, Rainford N, Donohue C, Fraser C, Sinha A, Dorling J, Gray J, McGuire W, Gamble C, Oddie SJ, PREVAIL trial team The Lancet, Child & Adolescent Health (2019)...