Are myocardial infarction-associated single-nucleotide polymorphisms associated with ischemic stroke?

Yu Ching Cheng, Christopher D. Anderson, Silvia Bione, Keith Keene, Jane M. Maguire, Michael Nalls, Asif Rasheed, Marion Zeginigg, John Attia, Ross Baker, Simona Barlera, Alessandro Biffi, Ebony Bookman, Thomas G. Brott, Robert D. Brown, Fang Chen, Wei Min Chen, Emilio Ciusani, John W. Cole, Lynelle CortelliniJohn Danesh, Kimberly Doheny, Luigi Ferrucci, Maria Grazia Franzosi, Philippe Frossard, Karen L. Furie, Jonathan Golledge, Graeme J. Hankey, Dena Hernandez, Elizabeth G. Holliday, Fang Chi Hsu, Jim Jannes, Ayeesha Kamal, Muhammad Saleem Khan, Steven J. Kittner, Simon A. Koblar, Martin Lewis, Lisa Lincz, Antonella Lisa, Mar Matarin, Pablo Moscato, Josyf C. Mychaleckyj, Eugenio A. Parati, Silvia Parolo, Elizabeth Pugh, Natalia S. Rost, Michael Schallert, Helena Schmidt, Rodney J. Scott, Jonathan W. Sturm, Sunaina Yadav, Moazzam Zaidi, Giorgio B. Boncoraglio, Christopher Royce Levi, James F. Meschia, Jonathan Rosand, Michele Sale, Danish Saleheen, Reinhold Schmidt, Pankaj Sharma, Bradford Worrall, Braxton D. Mitchell

Research output: Contribution to journalArticle

Abstract

Background and Purpose-Ischemic stroke (IS) shares many common risk factors with coronary artery disease (CAD). We hypothesized that genetic variants associated with myocardial infarction (MI) or CAD may be similarly involved in the etiology of IS. To test this hypothesis, we evaluated whether single-nucleotide polymorphisms (SNPs) at 11 different loci recently associated with MI or CAD through genome-wide association studies were associated with IS. Methods-Meta-analyses of the associations between the 11 MI-associated SNPs and IS were performed using 6865 cases and 11 395 control subjects recruited from 9 studies. SNPs were either genotyped directly or imputed; in a few cases a surrogate SNP in high linkage disequilibrium was chosen. Logistic regression was performed within each study to obtain study-specific βs and standard errors. Meta-analysis was conducted using an inverse variance weighted approach assuming a random effect model. Results-Despite having power to detect odds ratio of 1.09-1.14 for overall IS and 1.20-1.32 for major stroke subtypes, none of the SNPs were significantly associated with overall IS and/or stroke subtypes after adjusting for multiple comparisons. Conclusions-Our results suggest that the major common loci associated with MI risk do not have effects of similar magnitude on overall IS but do not preclude moderate associations restricted to specific IS subtypes. Disparate mechanisms may be critical in the development of acute ischemic coronary and cerebrovascular events.

Original languageEnglish (US)
Pages (from-to)980-986
Number of pages7
JournalStroke
Volume43
Issue number4
DOIs
StatePublished - Apr 2012

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Single Nucleotide Polymorphism
Stroke
Myocardial Infarction
Meta-Analysis
Genome-Wide Association Study
Linkage Disequilibrium
Coronary Artery Disease
Logistic Models
Odds Ratio

Keywords

  • cerebral infarct
  • genetics
  • ischemia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing

Cite this

Cheng, Y. C., Anderson, C. D., Bione, S., Keene, K., Maguire, J. M., Nalls, M., ... Mitchell, B. D. (2012). Are myocardial infarction-associated single-nucleotide polymorphisms associated with ischemic stroke? Stroke, 43(4), 980-986. https://doi.org/10.1161/STROKEAHA.111.632075

Are myocardial infarction-associated single-nucleotide polymorphisms associated with ischemic stroke? / Cheng, Yu Ching; Anderson, Christopher D.; Bione, Silvia; Keene, Keith; Maguire, Jane M.; Nalls, Michael; Rasheed, Asif; Zeginigg, Marion; Attia, John; Baker, Ross; Barlera, Simona; Biffi, Alessandro; Bookman, Ebony; Brott, Thomas G.; Brown, Robert D.; Chen, Fang; Chen, Wei Min; Ciusani, Emilio; Cole, John W.; Cortellini, Lynelle; Danesh, John; Doheny, Kimberly; Ferrucci, Luigi; Franzosi, Maria Grazia; Frossard, Philippe; Furie, Karen L.; Golledge, Jonathan; Hankey, Graeme J.; Hernandez, Dena; Holliday, Elizabeth G.; Hsu, Fang Chi; Jannes, Jim; Kamal, Ayeesha; Khan, Muhammad Saleem; Kittner, Steven J.; Koblar, Simon A.; Lewis, Martin; Lincz, Lisa; Lisa, Antonella; Matarin, Mar; Moscato, Pablo; Mychaleckyj, Josyf C.; Parati, Eugenio A.; Parolo, Silvia; Pugh, Elizabeth; Rost, Natalia S.; Schallert, Michael; Schmidt, Helena; Scott, Rodney J.; Sturm, Jonathan W.; Yadav, Sunaina; Zaidi, Moazzam; Boncoraglio, Giorgio B.; Levi, Christopher Royce; Meschia, James F.; Rosand, Jonathan; Sale, Michele; Saleheen, Danish; Schmidt, Reinhold; Sharma, Pankaj; Worrall, Bradford; Mitchell, Braxton D.

In: Stroke, Vol. 43, No. 4, 04.2012, p. 980-986.

Research output: Contribution to journalArticle

Cheng, YC, Anderson, CD, Bione, S, Keene, K, Maguire, JM, Nalls, M, Rasheed, A, Zeginigg, M, Attia, J, Baker, R, Barlera, S, Biffi, A, Bookman, E, Brott, TG, Brown, RD, Chen, F, Chen, WM, Ciusani, E, Cole, JW, Cortellini, L, Danesh, J, Doheny, K, Ferrucci, L, Franzosi, MG, Frossard, P, Furie, KL, Golledge, J, Hankey, GJ, Hernandez, D, Holliday, EG, Hsu, FC, Jannes, J, Kamal, A, Khan, MS, Kittner, SJ, Koblar, SA, Lewis, M, Lincz, L, Lisa, A, Matarin, M, Moscato, P, Mychaleckyj, JC, Parati, EA, Parolo, S, Pugh, E, Rost, NS, Schallert, M, Schmidt, H, Scott, RJ, Sturm, JW, Yadav, S, Zaidi, M, Boncoraglio, GB, Levi, CR, Meschia, JF, Rosand, J, Sale, M, Saleheen, D, Schmidt, R, Sharma, P, Worrall, B & Mitchell, BD 2012, 'Are myocardial infarction-associated single-nucleotide polymorphisms associated with ischemic stroke?', Stroke, vol. 43, no. 4, pp. 980-986. https://doi.org/10.1161/STROKEAHA.111.632075
Cheng, Yu Ching ; Anderson, Christopher D. ; Bione, Silvia ; Keene, Keith ; Maguire, Jane M. ; Nalls, Michael ; Rasheed, Asif ; Zeginigg, Marion ; Attia, John ; Baker, Ross ; Barlera, Simona ; Biffi, Alessandro ; Bookman, Ebony ; Brott, Thomas G. ; Brown, Robert D. ; Chen, Fang ; Chen, Wei Min ; Ciusani, Emilio ; Cole, John W. ; Cortellini, Lynelle ; Danesh, John ; Doheny, Kimberly ; Ferrucci, Luigi ; Franzosi, Maria Grazia ; Frossard, Philippe ; Furie, Karen L. ; Golledge, Jonathan ; Hankey, Graeme J. ; Hernandez, Dena ; Holliday, Elizabeth G. ; Hsu, Fang Chi ; Jannes, Jim ; Kamal, Ayeesha ; Khan, Muhammad Saleem ; Kittner, Steven J. ; Koblar, Simon A. ; Lewis, Martin ; Lincz, Lisa ; Lisa, Antonella ; Matarin, Mar ; Moscato, Pablo ; Mychaleckyj, Josyf C. ; Parati, Eugenio A. ; Parolo, Silvia ; Pugh, Elizabeth ; Rost, Natalia S. ; Schallert, Michael ; Schmidt, Helena ; Scott, Rodney J. ; Sturm, Jonathan W. ; Yadav, Sunaina ; Zaidi, Moazzam ; Boncoraglio, Giorgio B. ; Levi, Christopher Royce ; Meschia, James F. ; Rosand, Jonathan ; Sale, Michele ; Saleheen, Danish ; Schmidt, Reinhold ; Sharma, Pankaj ; Worrall, Bradford ; Mitchell, Braxton D. / Are myocardial infarction-associated single-nucleotide polymorphisms associated with ischemic stroke?. In: Stroke. 2012 ; Vol. 43, No. 4. pp. 980-986.
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title = "Are myocardial infarction-associated single-nucleotide polymorphisms associated with ischemic stroke?",
abstract = "Background and Purpose-Ischemic stroke (IS) shares many common risk factors with coronary artery disease (CAD). We hypothesized that genetic variants associated with myocardial infarction (MI) or CAD may be similarly involved in the etiology of IS. To test this hypothesis, we evaluated whether single-nucleotide polymorphisms (SNPs) at 11 different loci recently associated with MI or CAD through genome-wide association studies were associated with IS. Methods-Meta-analyses of the associations between the 11 MI-associated SNPs and IS were performed using 6865 cases and 11 395 control subjects recruited from 9 studies. SNPs were either genotyped directly or imputed; in a few cases a surrogate SNP in high linkage disequilibrium was chosen. Logistic regression was performed within each study to obtain study-specific βs and standard errors. Meta-analysis was conducted using an inverse variance weighted approach assuming a random effect model. Results-Despite having power to detect odds ratio of 1.09-1.14 for overall IS and 1.20-1.32 for major stroke subtypes, none of the SNPs were significantly associated with overall IS and/or stroke subtypes after adjusting for multiple comparisons. Conclusions-Our results suggest that the major common loci associated with MI risk do not have effects of similar magnitude on overall IS but do not preclude moderate associations restricted to specific IS subtypes. Disparate mechanisms may be critical in the development of acute ischemic coronary and cerebrovascular events.",
keywords = "cerebral infarct, genetics, ischemia",
author = "Cheng, {Yu Ching} and Anderson, {Christopher D.} and Silvia Bione and Keith Keene and Maguire, {Jane M.} and Michael Nalls and Asif Rasheed and Marion Zeginigg and John Attia and Ross Baker and Simona Barlera and Alessandro Biffi and Ebony Bookman and Brott, {Thomas G.} and Brown, {Robert D.} and Fang Chen and Chen, {Wei Min} and Emilio Ciusani and Cole, {John W.} and Lynelle Cortellini and John Danesh and Kimberly Doheny and Luigi Ferrucci and Franzosi, {Maria Grazia} and Philippe Frossard and Furie, {Karen L.} and Jonathan Golledge and Hankey, {Graeme J.} and Dena Hernandez and Holliday, {Elizabeth G.} and Hsu, {Fang Chi} and Jim Jannes and Ayeesha Kamal and Khan, {Muhammad Saleem} and Kittner, {Steven J.} and Koblar, {Simon A.} and Martin Lewis and Lisa Lincz and Antonella Lisa and Mar Matarin and Pablo Moscato and Mychaleckyj, {Josyf C.} and Parati, {Eugenio A.} and Silvia Parolo and Elizabeth Pugh and Rost, {Natalia S.} and Michael Schallert and Helena Schmidt and Scott, {Rodney J.} and Sturm, {Jonathan W.} and Sunaina Yadav and Moazzam Zaidi and Boncoraglio, {Giorgio B.} and Levi, {Christopher Royce} and Meschia, {James F.} and Jonathan Rosand and Michele Sale and Danish Saleheen and Reinhold Schmidt and Pankaj Sharma and Bradford Worrall and Mitchell, {Braxton D.}",
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T1 - Are myocardial infarction-associated single-nucleotide polymorphisms associated with ischemic stroke?

AU - Cheng, Yu Ching

AU - Anderson, Christopher D.

AU - Bione, Silvia

AU - Keene, Keith

AU - Maguire, Jane M.

AU - Nalls, Michael

AU - Rasheed, Asif

AU - Zeginigg, Marion

AU - Attia, John

AU - Baker, Ross

AU - Barlera, Simona

AU - Biffi, Alessandro

AU - Bookman, Ebony

AU - Brott, Thomas G.

AU - Brown, Robert D.

AU - Chen, Fang

AU - Chen, Wei Min

AU - Ciusani, Emilio

AU - Cole, John W.

AU - Cortellini, Lynelle

AU - Danesh, John

AU - Doheny, Kimberly

AU - Ferrucci, Luigi

AU - Franzosi, Maria Grazia

AU - Frossard, Philippe

AU - Furie, Karen L.

AU - Golledge, Jonathan

AU - Hankey, Graeme J.

AU - Hernandez, Dena

AU - Holliday, Elizabeth G.

AU - Hsu, Fang Chi

AU - Jannes, Jim

AU - Kamal, Ayeesha

AU - Khan, Muhammad Saleem

AU - Kittner, Steven J.

AU - Koblar, Simon A.

AU - Lewis, Martin

AU - Lincz, Lisa

AU - Lisa, Antonella

AU - Matarin, Mar

AU - Moscato, Pablo

AU - Mychaleckyj, Josyf C.

AU - Parati, Eugenio A.

AU - Parolo, Silvia

AU - Pugh, Elizabeth

AU - Rost, Natalia S.

AU - Schallert, Michael

AU - Schmidt, Helena

AU - Scott, Rodney J.

AU - Sturm, Jonathan W.

AU - Yadav, Sunaina

AU - Zaidi, Moazzam

AU - Boncoraglio, Giorgio B.

AU - Levi, Christopher Royce

AU - Meschia, James F.

AU - Rosand, Jonathan

AU - Sale, Michele

AU - Saleheen, Danish

AU - Schmidt, Reinhold

AU - Sharma, Pankaj

AU - Worrall, Bradford

AU - Mitchell, Braxton D.

PY - 2012/4

Y1 - 2012/4

N2 - Background and Purpose-Ischemic stroke (IS) shares many common risk factors with coronary artery disease (CAD). We hypothesized that genetic variants associated with myocardial infarction (MI) or CAD may be similarly involved in the etiology of IS. To test this hypothesis, we evaluated whether single-nucleotide polymorphisms (SNPs) at 11 different loci recently associated with MI or CAD through genome-wide association studies were associated with IS. Methods-Meta-analyses of the associations between the 11 MI-associated SNPs and IS were performed using 6865 cases and 11 395 control subjects recruited from 9 studies. SNPs were either genotyped directly or imputed; in a few cases a surrogate SNP in high linkage disequilibrium was chosen. Logistic regression was performed within each study to obtain study-specific βs and standard errors. Meta-analysis was conducted using an inverse variance weighted approach assuming a random effect model. Results-Despite having power to detect odds ratio of 1.09-1.14 for overall IS and 1.20-1.32 for major stroke subtypes, none of the SNPs were significantly associated with overall IS and/or stroke subtypes after adjusting for multiple comparisons. Conclusions-Our results suggest that the major common loci associated with MI risk do not have effects of similar magnitude on overall IS but do not preclude moderate associations restricted to specific IS subtypes. Disparate mechanisms may be critical in the development of acute ischemic coronary and cerebrovascular events.

AB - Background and Purpose-Ischemic stroke (IS) shares many common risk factors with coronary artery disease (CAD). We hypothesized that genetic variants associated with myocardial infarction (MI) or CAD may be similarly involved in the etiology of IS. To test this hypothesis, we evaluated whether single-nucleotide polymorphisms (SNPs) at 11 different loci recently associated with MI or CAD through genome-wide association studies were associated with IS. Methods-Meta-analyses of the associations between the 11 MI-associated SNPs and IS were performed using 6865 cases and 11 395 control subjects recruited from 9 studies. SNPs were either genotyped directly or imputed; in a few cases a surrogate SNP in high linkage disequilibrium was chosen. Logistic regression was performed within each study to obtain study-specific βs and standard errors. Meta-analysis was conducted using an inverse variance weighted approach assuming a random effect model. Results-Despite having power to detect odds ratio of 1.09-1.14 for overall IS and 1.20-1.32 for major stroke subtypes, none of the SNPs were significantly associated with overall IS and/or stroke subtypes after adjusting for multiple comparisons. Conclusions-Our results suggest that the major common loci associated with MI risk do not have effects of similar magnitude on overall IS but do not preclude moderate associations restricted to specific IS subtypes. Disparate mechanisms may be critical in the development of acute ischemic coronary and cerebrovascular events.

KW - cerebral infarct

KW - genetics

KW - ischemia

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