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https://doi.org/10.1371/journal.pone.0099798
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dc.title | Associations of NINJ2 sequence variants with incident ischemic stroke in the Cohorts for Heart and Aging in Genomic Epidemiology (CHARGE) consortium | |
dc.contributor.author | Bis J.C. | |
dc.contributor.author | DeStefano A. | |
dc.contributor.author | Liu X. | |
dc.contributor.author | Brody J.A. | |
dc.contributor.author | Choi S.H. | |
dc.contributor.author | Verhaaren B.F.J. | |
dc.contributor.author | Debette S. | |
dc.contributor.author | Ikram M.A. | |
dc.contributor.author | Shahar E. | |
dc.contributor.author | Butler Jr. K.R. | |
dc.contributor.author | Gottesman R.F. | |
dc.contributor.author | Muzny D. | |
dc.contributor.author | Kovar C.L. | |
dc.contributor.author | Psaty B.M. | |
dc.contributor.author | Hofman A. | |
dc.contributor.author | Lumley T. | |
dc.contributor.author | Gupta M. | |
dc.contributor.author | Wolf P.A. | |
dc.contributor.author | Van Duijn C. | |
dc.contributor.author | Gibbs R.A. | |
dc.contributor.author | Mosley T.H. | |
dc.contributor.author | Longstreth Jr. W.T. | |
dc.contributor.author | Boerwinkle E. | |
dc.contributor.author | Seshadri S. | |
dc.contributor.author | Fornage M. | |
dc.date.accessioned | 2019-11-05T00:35:58Z | |
dc.date.available | 2019-11-05T00:35:58Z | |
dc.date.issued | 2014 | |
dc.identifier.citation | Bis J.C., DeStefano A., Liu X., Brody J.A., Choi S.H., Verhaaren B.F.J., Debette S., Ikram M.A., Shahar E., Butler Jr. K.R., Gottesman R.F., Muzny D., Kovar C.L., Psaty B.M., Hofman A., Lumley T., Gupta M., Wolf P.A., Van Duijn C., Gibbs R.A., Mosley T.H., Longstreth Jr. W.T., Boerwinkle E., Seshadri S., Fornage M. (2014). Associations of NINJ2 sequence variants with incident ischemic stroke in the Cohorts for Heart and Aging in Genomic Epidemiology (CHARGE) consortium. PLoS ONE 9 (6) : e99798. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0099798 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/161403 | |
dc.description.abstract | Background: Stroke, the leading neurologic cause of death and disability, has a substantial genetic component. We previously conducted a genome-wide association study (GWAS) in four prospective studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and demonstrated that sequence variants near the NINJ2 gene are associated with incident ischemic stroke. Here, we sought to fine-map functional variants in the region and evaluate the contribution of rare variants to ischemic stroke risk. Methods and Results: We sequenced 196 kb around NINJ2 on chromosome 12p13 among 3,986 European ancestry participants, including 475 ischemic stroke cases, from the Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, and Framingham Heart Study. Meta-analyses of single-variant tests for 425 common variants (minor allele frequency [MAF] ≥1%) confirmed the original GWAS results and identified an independent intronic variant, rs34166160 (MAF = 0.012), most significantly associated with incident ischemic stroke (HR = 1.80, p = 0.0003). Aggregating 278 putatively-functional variants with MAF≤1% using count statistics, we observed a nominally statistically significant association, with the burden of rare NINJ2 variants contributing to decreased ischemic stroke incidence (HR = 0.81; p = 0.026). Conclusion: Common and rare variants in the NINJ2 region were nominally associated with incident ischemic stroke among a subset of CHARGE participants. Allelic heterogeneity at this locus, caused by multiple rare, low frequency, and common variants with disparate effects on risk, may explain the difficulties in replicating the original GWAS results. Additional studies that take into account the complex allelic architecture at this locus are needed to confirm these findings. © 2014 Bis et al. | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | Unpaywall 20191101 | |
dc.subject | adult | |
dc.subject | aged | |
dc.subject | article | |
dc.subject | atherosclerosis | |
dc.subject | brain ischemia | |
dc.subject | cardiovascular disease | |
dc.subject | controlled study | |
dc.subject | female | |
dc.subject | gene frequency | |
dc.subject | gene function | |
dc.subject | gene locus | |
dc.subject | gene mapping | |
dc.subject | gene sequence | |
dc.subject | genetic association | |
dc.subject | genetic heterogeneity | |
dc.subject | genetic variability | |
dc.subject | human | |
dc.subject | incidence | |
dc.subject | intron | |
dc.subject | major clinical study | |
dc.subject | male | |
dc.subject | medical research | |
dc.subject | middle aged | |
dc.subject | NINJ2 gene | |
dc.subject | risk assessment | |
dc.subject | Caucasian | |
dc.subject | DNA sequence | |
dc.subject | genetic association study | |
dc.subject | genetics | |
dc.subject | ischemia | |
dc.subject | meta analysis | |
dc.subject | Myocardial Infarction | |
dc.subject | procedures | |
dc.subject | prospective study | |
dc.subject | single nucleotide polymorphism | |
dc.subject | nerve cell adhesion molecule | |
dc.subject | NINJ2 protein, human | |
dc.subject | Cell Adhesion Molecules, Neuronal | |
dc.subject | European Continental Ancestry Group | |
dc.subject | Female | |
dc.subject | Genetic Association Studies | |
dc.subject | Genetic Heterogeneity | |
dc.subject | Humans | |
dc.subject | Introns | |
dc.subject | Ischemia | |
dc.subject | Male | |
dc.subject | Myocardial Infarction | |
dc.subject | Polymorphism, Single Nucleotide | |
dc.subject | Prospective Studies | |
dc.subject | Sequence Analysis, DNA | |
dc.type | Article | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.description.doi | 10.1371/journal.pone.0099798 | |
dc.description.sourcetitle | PLoS ONE | |
dc.description.volume | 9 | |
dc.description.issue | 6 | |
dc.description.page | e99798 | |
dc.published.state | Published | |
Appears in Collections: | Staff Publications Elements |
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