TY - JOUR
T1 - A replication study of genetic risk loci for ischemic stroke in a Dutch population
T2 - A case-control study
AU - Hauer, Allard J.
AU - Pulit, Sara L.
AU - Van Den Berg, Leonard H.
AU - De Bakker, Paul I.W.
AU - Veldink, Jan H.
AU - Ruigrok, Ynte M.
AU - Klijn, Catharina J.M.
AU - Algra, Ale
AU - Van Dijk, Ewoud J.
AU - Koudstaal, Peter J.
AU - Luijckx, Gert Jan
AU - Nederkoorn, Paul J.
AU - Oostenbrugge, Robert J.
AU - Visser, Marieke C.
AU - Wermer, Marieke J H
AU - Kappelle, L. Jaap
N1 - Funding Information:
This study was funded by Parelsnoer Institute (PSI), which was co-financed by the Dutch Government, the Dutch Federation of University Medical Centers (UMC) and the eight UMCs (from 2007–2011). The continuation of the PSI is financed by the UMCs. Y.M. Ruigrok was supported by a clinical fellowship grant of the Netherlands Organization for Scientific Research (NWO) (project no. 40-00703-98-13533). C.J.M. Klijn is supported by a clinical established investigator grant from the Dutch Heart Foundation (2012T077), and an ASPASIA grant from The Netherlands Organisation for Health Research and Development, ZonMw (grant number 015008048).
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/9/22
Y1 - 2017/9/22
N2 - We aimed to replicate reported associations of 10 SNPs at eight distinct loci with overall ischemic stroke (IS) and its subtypes in an independent cohort of Dutch IS patients. We included 1,375 IS patients enrolled in a prospective multicenter hospital-based cohort in the Netherlands, and 1,533 population-level controls of Dutch descent. We tested these SNPs for association with overall IS and its subtypes (large artery atherosclerosis, small vessel disease and cardioembolic stroke (CE), as classified by TOAST) using an additive multivariable logistic regression model, adjusting for age and sex. We obtained odds ratios (OR) with 95% confidence intervals (95% CI) for the risk allele of each SNP analyzed and exact p-values by permutation. We confirmed the association at 4q25 (PITX2) (OR 1.43; 95% CI, 1.13-1.81, p = 0.029) and 16q22 (ZFHX3) (OR 1.62; 95% CI, 1.26-2.07, p = 0.001) as risk loci for CE. Locus 16q22 was also associated with overall IS (OR 1.24; 95% CI, 1.08-1.42, p = 0.016). Other loci previously associated with IS and/or its subtypes were not confirmed. In conclusion, we validated two loci (4q25, 16q22) associated with CE. In addition, our study may suggest that the association of locus 16q22 may not be limited to CE, but also includes overall IS.
AB - We aimed to replicate reported associations of 10 SNPs at eight distinct loci with overall ischemic stroke (IS) and its subtypes in an independent cohort of Dutch IS patients. We included 1,375 IS patients enrolled in a prospective multicenter hospital-based cohort in the Netherlands, and 1,533 population-level controls of Dutch descent. We tested these SNPs for association with overall IS and its subtypes (large artery atherosclerosis, small vessel disease and cardioembolic stroke (CE), as classified by TOAST) using an additive multivariable logistic regression model, adjusting for age and sex. We obtained odds ratios (OR) with 95% confidence intervals (95% CI) for the risk allele of each SNP analyzed and exact p-values by permutation. We confirmed the association at 4q25 (PITX2) (OR 1.43; 95% CI, 1.13-1.81, p = 0.029) and 16q22 (ZFHX3) (OR 1.62; 95% CI, 1.26-2.07, p = 0.001) as risk loci for CE. Locus 16q22 was also associated with overall IS (OR 1.24; 95% CI, 1.08-1.42, p = 0.016). Other loci previously associated with IS and/or its subtypes were not confirmed. In conclusion, we validated two loci (4q25, 16q22) associated with CE. In addition, our study may suggest that the association of locus 16q22 may not be limited to CE, but also includes overall IS.
UR - http://www.scopus.com/inward/record.url?scp=85029740288&partnerID=8YFLogxK
U2 - 10.1038/s41598-017-07404-4
DO - 10.1038/s41598-017-07404-4
M3 - Article
C2 - 28939865
AN - SCOPUS:85029740288
SN - 2045-2322
VL - 7
SP - 1
EP - 5
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 12175
ER -