RIFINs are adhesins implicated in severe Plasmodium falciparum malaria.
Suchi Goel, Mia Palmkvist, Kirsten Moll, Nicolas Joannin, Patricia Lara, Reetesh R Akhouri, Nasim Moradi, Karin Öjemalm, Mattias Westman, Davide Angeletti, Hanna Kjellin, Janne Lehtiö, Ola Blixt, Lars Ideström, Carl G Gahmberg, Jill R Storry, Annika K Hult, Martin L Olsson, Gunnar von Heijne, IngMarie Nilsson & Mats Wahlgren
Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies
Original TextDr Muredach P Reilly MB a b ?, Mingyao Li PhD c ?, Jing He PhD c, Jane F Ferguson PhD a, Ioannis M Stylianou PhD b, Nehal N Mehta MD a b, Mary Susan Burnett PhD d, Joseph M Devaney PhD d, Christopher W Knouff MD e, Prof John R Thompson PhD f, Benjamin D Horne PhD h i, Alexandre FR Stewart PhD k, Themistocles L Assimes MD l, Philipp S Wild MD m, Hooman Allayee PhD n, Patrick Linsel Nitschke MD o, Riyaz S Patel MD p, Nicola Martinelli MD q, Prof Domenico Girelli MD q, Prof Arshed A Quyyumi MD p, Prof Jeffrey L Anderson MD h j, Prof Jeanette Erdmann PhD o, Alistair S Hall MD r, Prof Heribert Schunkert MD o, Prof Thomas Quertermous MD l, Prof Stefan Blankenberg MD m, Prof Stanley L Hazen PhD s, Prof Robert Roberts MD k, Sekar Kathiresan MD t u v w, Prof Nilesh J Samani MD g x, Prof Stephen E Epstein MD d, Prof Daniel J Rader MD a b, Myocardial Infarction Genetics Consortium?Wellcome Trust Case Control Consortium?
Summary
Background
We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis.
Methods
We did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12 393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644).
Findings
In the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4·98×10?13). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7·62×10?9). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against myocardial infarction.
Interpretation
Our findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD.
Funding
The PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix.
ABO blood type, factor VIII, and incident cognitive impairment in the REGARDS cohort
Kristine S. Alexander, PhD, MCR, Neil A. Zakai, MD, MSc, Sarah Gillett, PhD, Leslie A. McClure, PhD, Virginia Wadley, PhD, Fred Unverzagt, PhD and Mary Cushman, MD, MSc
