Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Default user image.

Olle Melander

Principal investigator

Default user image.

Exome array analysis of ischaemic stroke : results from a southern Swedish study

Author

  • M Söderholm
  • P Almgren
  • K Jood
  • T M Stanne
  • Mats Olsson
  • A Ilinca
  • E Lorentzen
  • B Norrving
  • G Engström
  • O Melander
  • C Jern
  • Arne Lindgren

Summary, in English

BACKGROUND AND PURPOSE: Genome-wide association (GWA) studies have identified a few risk loci for ischaemic stroke, but these variants explain only a small part of the genetic contribution to the disease. Coding variants associated with amino acid substitutions or premature termination of protein synthesis could have a large effect on disease risk. We performed an exome array analysis for ischaemic stroke.

METHODS: Patients with ischaemic stroke (n = 2385) and control subjects (n = 6077) from three Swedish studies were genotyped with the Illumina HumanOmniExpressExome BeadChip. Single-variant association analysis and gene-based tests were performed of exome variants with minor allele frequency of < 5%. A separate GWA analysis was also performed, based on 700 000 genotyped common markers and subsequent imputation.

RESULTS: No exome variant or gene was significantly associated with all ischaemic stroke after Bonferroni correction (all P > 1.8 × 10(-6) for single-variant and >4.15 × 10(-6) for gene-based analysis). The strongest association in single-variant analysis was found for a missense variant in the DNAH11 gene (rs143362381; P = 5.01 × 10(-6) ). In gene-based tests, the strongest association was for the ZBTB20 gene (P = 7.9 × 10(-5) ). The GWA analysis showed that the sample was homogenous (median genomic inflation factor = 1.006). No genome-wide significant association with overall ischaemic stroke risk was found. However, previously reported associations for the PITX2 and ZFHX3 gene loci with cardioembolic stroke subtype were replicated (P = 7 × 10(-15) and 6 × 10(-3) ).

CONCLUSIONS: This exome array analysis did not identify any single variants or genes reaching the pre-defined significance level for association with ischaemic stroke. Further studies on exome variants should be performed in even larger, well-defined and subtyped samples.

Department/s

  • Cardiovascular Research - Epidemiology
  • Genomics, Diabetes and Endocrinology
  • Neurology, Lund
  • Cardiovascular Research - Hypertension
  • Clinical Stroke Research Group
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2016-07-29

Language

English

Pages

1722-1728

Publication/Series

European Journal of Neurology

Volume

23

Issue

12

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Neurosciences

Keywords

  • stroke
  • exome array

Status

Published

Research group

  • Cardiovascular Research - Epidemiology
  • Genomics, Diabetes and Endocrinology
  • Cardiovascular Research - Hypertension
  • Clinical Stroke Research Group

ISBN/ISSN/Other

  • ISSN: 1351-5101