Correction to: Polygenic Risk for Depression Increases Risk of Ischemic Stroke From the Stroke Genetics Network Study.

Abstract

HomeStrokeVol. 50, No. 1Correction to: Polygenic Risk for Depression Increases Risk of Ischemic Stroke From the Stroke Genetics Network Study Free AccessCorrectionPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCorrectionPDF/EPUBCorrection to: Polygenic Risk for Depression Increases Risk of Ischemic Stroke From the Stroke Genetics Network Study Originally published24 Dec 2018https://doi.org/10.1161/STR.0000000000000182Stroke. 2019;50:e24–e25This article corrects the followingPolygenic Risk for Depression Increases Risk of Ischemic StrokeIn the article by Wassertheil-Smoller et al, “Polygenic Risk for Depression Increases Risk of Ischemic Stroke From the Stroke Genetics Network Study,” which published online February 8, 2018, and appeared in the March 2018 issue of the journal (Stroke. 2018;49:543–548. doi: 10.1161/STROKEAHA.117.018857) corrections are needed.The authors generated a polygenic risk score for major depressive disorder based on the 2013 genome-wide association study (GWAS) results from the Psychiatric Genetic Consortium (PGC) and used this score to test the hypothesis that genetic risk for depression was associated with ischemic stroke in 16,000 cases from the Stroke Genetics Network (SiGN). The polygenic risk score (PRS) analysis revealed a modest association of the PRS with stroke risk, indicating genetic overlap between depression and stroke, particularly for small artery stroke.Following the publication of the article, the PGC released much expanded GWAS results in 2018 of depression based on 59,851 cases and 113,154 controls.1 While doing a subsequent analysis of these more recent data undertaken to determine if the original findings could be confirmed with this larger sample, the authors discovered a programming error made by an analyst at the SiGN Data Center. The numerical results, including effect sizes provided in the article, are incorrect.A corrected reanalysis of the 2013 data does not show association of the PRS with stroke, although the new, larger analysis supports most, though not all, of the original conclusions. Consistent with the published article, the new evidence supports genetic overlap between depression and stroke in this larger sample. In stroke subtype analyses however, the original conclusions indicated that both European and African ancestry samples showed association of depression PRS with elevated risk of small artery occlusion (SAO), while the corrected 2018 analysis indicates that only European ancestry samples show the elevated risk of SAO. The published conclusions indicated that only in African ancestry persons was there an association of depression PRS with higher risk of large artery atherosclerosis (LAA) while the conclusions based on the new evidence indicate that depression PRS is associated with higher risk of LAA in both European and African ancestry samples. Depression PRS was not significantly associated with cardioembolic stroke in either European or African ancestry persons.All of the data in Tables 1–4 have been changed to reflect the more recent analysis. The number of cases and controls were updated. The new tables in the paper based on the new data are shown below. Note that in the online supplement, results for CCSc algorithm and the TOAST results have been updated and are correct and accurate.Table 1. Relationship Between Polygenic Risk for Depression and All Ischemic Stroke Using 8 Polygenic Risk Scores for Different Inclusion Criteria (PT) Into the PRS European Ancestry Adults (N = 12,577 Cases, 25,643 Controls)PTNo. of SNPs Included in PRSBetasSEP Values for Betas0.00122760.02880.00850.0006480.01132810.01640.00404.36E-050.05485570.00930.00221.58E-050.1858100.00780.00174.45E-060.21532740.00600.00148.53E-060.32146670.00490.00124.43E-050.42723220.00490.00111.02E-050.53260880.00370.00100.000347PT: p-value threshold for SNP inclusion into the PRS. Betas relates PRS to stroke subtype, per unit of PRS.Table 2. Relationship Between Polygenic Risk for Depression and All Ischemic Stroke Using 8 Polygenic Risk Scores for Different Inclusion Criteria (PT) Into the PRS African Ancestry Adults (N = 1353 cases, 2383 Controls)PTNo. of SNPs Included in PRSBetasSEP Values for Betas0.00134490.01100.01630.4980.01193500.00290.00550.5950.05696890.00220.00160.1710.11215520.00200.00110.0690.22118520.00140.00070.0630.32914000.00150.00070.0280.43644340.00110.00060.0840.54318380.00100.00060.064Table 3. Relationship Between PRS Based on 85,810 SNP’s With Inclusion Criterion Into PRS of PT <.1, by CCSp Stroke Subtype for European Ancestry AdultsPhenotype (CCSp)Total No. of CasesTotal No. of ControlsBetasSEP Value for BetasOR (95% CI) for Stroke, per 1 SD of PRS=eBeta*SDAll stroke12577256430.00780.00174.45E-061.05 (1.03–1.08)LAA2229256430.01050.00330.0021.07 (1.03–1.12)SAO2029256430.01250.00342.41E-041.09 (1.04–1.14)CE3400256430.00480.00280.0871.03 (1.00–1.07)Other612256430.00670.00620.2811.05 (0.96–1.13)Crypto963256430.00510.00500.3101.03 (0.97–1.10)CCSp is the Causative Classification System - phenotypic.Betas relates PRS to stroke subtype, per unit of PRS.Table 4. Relationship Between PRS Based on 121,552 SNPs With Inclusion Criterion Into PRS of PT <.1, by CCSp Stroke Subtype for African AncestryPhenotype (CCSp)Total No. of CasesTotal No. of ControlsBetasSEP Value for BetasOR (95% CI) for Stroke, per 1 SD of PRS=eBeta*SDAll stroke135323830.00200.00110.06871.07 (1.00–1.14)LAA22023830.00540.00220.01641.19 (1.03–1.37)SAO39023830.00090.00170.57711.03 (0.93–1.15)CE20823830.00040.00230.86231.01 (0.88–1.17)Other10623830.00210.00320.50391.07 (0.88–1.31)Crypto13323830.00210.00280.44821.07 (0.90–1.27)CCSp is the Causative Classification System – phenotypic.Betas relates PRS to stroke subtype, per unit of PRS.CCSp is the Causative Classification System – phenotypic.AcknowledgmentsThe authors would like to acknowledge the substantial contributions of Mr Brady Gaynor for his analysis of the PGC 2018 data. Previous Back to top Next FiguresReferencesRelatedDetailsCited By Cai H, Cai B, Zhang H, Sun W, Wang Y, Zhou S, Ye Z, Zhang Z and Liang J (2019) Major depression and small vessel stroke: a Mendelian randomization analysis, Journal of Neurology, 10.1007/s00415-019-09511-w, 266:11, (2859-2866), Online publication date: 1-Nov-2019. Related articlesPolygenic Risk for Depression Increases Risk of Ischemic StrokeSylvia Wassertheil-Smoller, et al. Stroke. 2018;49:543-548 January 2019Vol 50, Issue 1 Advertisement Article InformationMetrics © 2018 American Heart Association, Inc.https://doi.org/10.1161/STR.0000000000000182PMID: 30582828 Originally publishedDecember 24, 2018 PDF download Advertisement