Association of the 9p21.3 locus with risk of first-ever myocardial infarction in pakistanis: Case-control study in south asia and updated meta-analysis of europeans

Danish Saleheen; Myriam Alexander; Asif Rasheed; David Wormser; Nicole Soranzo; Naomi Hammond; Adam Butterworth; Moazzam Zaidi; Philip Haycock; Suzannah Bumpstead; Simon Potter; Hannah Blackburn; Emma Gray; Emanuele Di Angelantonio; Stephen Kaptoge; Nabi Shah; Maria Samuel; Ahmedyar Janjua; Nasir Sheikh; Shajjia Razi Haider; Muhammed Murtaza; Usman Ahmad; Abdul Hakeem; Muhammad Ali Memon; Nadeem Hayat Mallick; Muhammad Azhar; Abdus Samad; Syed Zahed Rasheed; Ali Raza Gardezi; Nazir Ahmed Memon; Abdul Ghaffar; Fazal Ur Rehman Memon; Khan Shah Zaman; Assadullah Kundi; Zia Yaqoob; Liaquat Ali Cheema; Nadeem Qamar; Azhar Faruqui; Rashid Jooma; Jawaid Hassan Niazi; Mustafa Hussain; Kishore Kumar; Asim Saleem; Kishwar Kumar; Muhammad Salman Daood; Fatima Memon; Aftab Alam Gul; Shahid Abbas; Junaid Zafar; Faisal Shahid; Zehra Memon; Shahzad Majeed Bhatti; Waleed Kayani; Syed Saadat Ali; Muhammad Fahim; Muhammad Ishaq; Philippe Frossard; Panos Deloukas; John Danesh

doi:10.1161/ATVBAHA.109.197210

Association of the 9p21.3 locus with risk of first-ever myocardial infarction in pakistanis: Case-control study in south asia and updated meta-analysis of europeans

Danish Saleheen, Myriam Alexander, Asif Rasheed, David Wormser, Nicole Soranzo, Naomi Hammond, Adam Butterworth, Moazzam Zaidi, Philip Haycock, Suzannah Bumpstead, Simon Potter, Hannah Blackburn, Emma Gray, Emanuele Di Angelantonio, Stephen Kaptoge, Nabi Shah, Maria Samuel, Ahmedyar Janjua, Nasir Sheikh, Shajjia Razi HaiderMuhammed Murtaza, Usman Ahmad, Abdul Hakeem, Muhammad Ali Memon, Nadeem Hayat Mallick, Muhammad Azhar, Abdus Samad, Syed Zahed Rasheed, Ali Raza Gardezi, Nazir Ahmed Memon, Abdul Ghaffar, Fazal Ur Rehman Memon, Khan Shah Zaman, Assadullah Kundi, Zia Yaqoob, Liaquat Ali Cheema, Nadeem Qamar, Azhar Faruqui, Rashid Jooma, Jawaid Hassan Niazi, Mustafa Hussain, Kishore Kumar, Asim Saleem, Kishwar Kumar, Muhammad Salman Daood, Fatima Memon, Aftab Alam Gul, Shahid Abbas, Junaid Zafar, Faisal Shahid, Zehra Memon, Shahzad Majeed Bhatti, Waleed Kayani, Syed Saadat Ali, Muhammad Fahim, Muhammad Ishaq, Philippe Frossard, Panos Deloukas, John Danesh

Research output: Contribution to journal › Article › peer-review

54 Citations (Scopus)

Abstract

Objective-: To examine variants at the 9p21 locus in a case-control study of acute myocardial infarction (MI) in Pakistanis and to perform an updated meta-analysis of published studies in people of European ancestry. Methods and Results-: A total of 1851 patients with first-ever confirmed MI and 1903 controls were genotyped for 89 tagging single-nucleotide polymorphisms at locus 9p21, including the lead variant (rs1333049) identified by the Wellcome Trust Case Control Consortium. Minor allele frequencies and extent of linkage disequilibrium observed in Pakistanis were broadly similar to those seen in Europeans. In the Pakistani study, 6 variants were associated with MI (P<10^-2) in the initial sample set, and in an additional 741 cases and 674 controls in whom further genotyping was performed for these variants. For Pakistanis, the odds ratio for MI was 1.13 (95% CI, 1.05 to 1.22; P=2×10^-3) for each copy of the C allele at rs1333049. In comparison, a meta-analysis of studies in Europeans yielded an odds ratio of 1.31 (95% CI, 1.26 to 1.37) for the same variant (P=1×10^-3 for heterogeneity). Meta-analyses of 23 variants, in up to 38 250 cases and 84 820 controls generally yielded higher values in Europeans than in Pakistanis. Conclusion-: To our knowledge, this study provides the first demonstration that variants at the 9p21 locus are significantly associated with MI risk in Pakistanis. However, association signals at this locus were weaker in Pakistanis than those in European studies.

Original language	English
Pages (from-to)	1467-1473
Number of pages	7
Journal	Arteriosclerosis, Thrombosis, and Vascular Biology
Volume	30
Issue number	7
DOIs	https://doi.org/10.1161/ATVBAHA.109.197210
Publication status	Published - Jul 2010
Externally published	Yes

Keywords

9p21
Pakistanis
South Asia
meta-analysis
myocardial infarction
risk factor

Access to Document

10.1161/ATVBAHA.109.197210

Cite this

Saleheen, D., Alexander, M., Rasheed, A., Wormser, D., Soranzo, N., Hammond, N., Butterworth, A., Zaidi, M., Haycock, P., Bumpstead, S., Potter, S., Blackburn, H., Gray, E., Di Angelantonio, E., Kaptoge, S., Shah, N., Samuel, M., Janjua, A., Sheikh, N., ... Danesh, J. (2010). Association of the 9p21.3 locus with risk of first-ever myocardial infarction in pakistanis: Case-control study in south asia and updated meta-analysis of europeans. Arteriosclerosis, Thrombosis, and Vascular Biology, 30(7), 1467-1473. https://doi.org/10.1161/ATVBAHA.109.197210

@article{1250f657d1f54a4e87840ddc71d7b937,

title = "Association of the 9p21.3 locus with risk of first-ever myocardial infarction in pakistanis: Case-control study in south asia and updated meta-analysis of europeans",

abstract = "Objective-: To examine variants at the 9p21 locus in a case-control study of acute myocardial infarction (MI) in Pakistanis and to perform an updated meta-analysis of published studies in people of European ancestry. Methods and Results-: A total of 1851 patients with first-ever confirmed MI and 1903 controls were genotyped for 89 tagging single-nucleotide polymorphisms at locus 9p21, including the lead variant (rs1333049) identified by the Wellcome Trust Case Control Consortium. Minor allele frequencies and extent of linkage disequilibrium observed in Pakistanis were broadly similar to those seen in Europeans. In the Pakistani study, 6 variants were associated with MI (P<10-2) in the initial sample set, and in an additional 741 cases and 674 controls in whom further genotyping was performed for these variants. For Pakistanis, the odds ratio for MI was 1.13 (95% CI, 1.05 to 1.22; P=2×10-3) for each copy of the C allele at rs1333049. In comparison, a meta-analysis of studies in Europeans yielded an odds ratio of 1.31 (95% CI, 1.26 to 1.37) for the same variant (P=1×10-3 for heterogeneity). Meta-analyses of 23 variants, in up to 38 250 cases and 84 820 controls generally yielded higher values in Europeans than in Pakistanis. Conclusion-: To our knowledge, this study provides the first demonstration that variants at the 9p21 locus are significantly associated with MI risk in Pakistanis. However, association signals at this locus were weaker in Pakistanis than those in European studies.",

keywords = "9p21, Pakistanis, South Asia, meta-analysis, myocardial infarction, risk factor",

author = "Danish Saleheen and Myriam Alexander and Asif Rasheed and David Wormser and Nicole Soranzo and Naomi Hammond and Adam Butterworth and Moazzam Zaidi and Philip Haycock and Suzannah Bumpstead and Simon Potter and Hannah Blackburn and Emma Gray and {Di Angelantonio}, Emanuele and Stephen Kaptoge and Nabi Shah and Maria Samuel and Ahmedyar Janjua and Nasir Sheikh and {Razi Haider}, Shajjia and Muhammed Murtaza and Usman Ahmad and Abdul Hakeem and {Ali Memon}, Muhammad and {Hayat Mallick}, Nadeem and Muhammad Azhar and Abdus Samad and Rasheed, {Syed Zahed} and Gardezi, {Ali Raza} and Memon, {Nazir Ahmed} and Abdul Ghaffar and Memon, {Fazal Ur Rehman} and Zaman, {Khan Shah} and Assadullah Kundi and Zia Yaqoob and {Ali Cheema}, Liaquat and Nadeem Qamar and Azhar Faruqui and Rashid Jooma and Niazi, {Jawaid Hassan} and Mustafa Hussain and Kishore Kumar and Asim Saleem and Kishwar Kumar and {Salman Daood}, Muhammad and Fatima Memon and {Alam Gul}, Aftab and Shahid Abbas and Junaid Zafar and Faisal Shahid and Zehra Memon and {Majeed Bhatti}, Shahzad and Waleed Kayani and {Saadat Ali}, Syed and Muhammad Fahim and Muhammad Ishaq and Philippe Frossard and Panos Deloukas and John Danesh",

year = "2010",

month = jul,

doi = "10.1161/ATVBAHA.109.197210",

language = "English",

volume = "30",

pages = "1467--1473",

journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",

issn = "1079-5642",

publisher = "Lippincott Williams and Wilkins Ltd.",

number = "7",

}

Saleheen, D, Alexander, M, Rasheed, A, Wormser, D, Soranzo, N, Hammond, N, Butterworth, A, Zaidi, M, Haycock, P, Bumpstead, S, Potter, S, Blackburn, H, Gray, E, Di Angelantonio, E, Kaptoge, S, Shah, N, Samuel, M, Janjua, A, Sheikh, N, Razi Haider, S, Murtaza, M, Ahmad, U, Hakeem, A, Ali Memon, M, Hayat Mallick, N, Azhar, M, Samad, A, Rasheed, SZ, Gardezi, AR, Memon, NA, Ghaffar, A, Memon, FUR, Zaman, KS, Kundi, A, Yaqoob, Z, Ali Cheema, L, Qamar, N, Faruqui, A, Jooma, R, Niazi, JH, Hussain, M, Kumar, K, Saleem, A, Kumar, K, Salman Daood, M, Memon, F, Alam Gul, A, Abbas, S, Zafar, J, Shahid, F, Memon, Z, Majeed Bhatti, S, Kayani, W, Saadat Ali, S, Fahim, M, Ishaq, M, Frossard, P, Deloukas, P & Danesh, J 2010, 'Association of the 9p21.3 locus with risk of first-ever myocardial infarction in pakistanis: Case-control study in south asia and updated meta-analysis of europeans', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 7, pp. 1467-1473. https://doi.org/10.1161/ATVBAHA.109.197210

Association of the 9p21.3 locus with risk of first-ever myocardial infarction in pakistanis: Case-control study in south asia and updated meta-analysis of europeans. / Saleheen, Danish; Alexander, Myriam; Rasheed, Asif et al.
In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 30, No. 7, 07.2010, p. 1467-1473.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Association of the 9p21.3 locus with risk of first-ever myocardial infarction in pakistanis

T2 - Case-control study in south asia and updated meta-analysis of europeans

AU - Saleheen, Danish

AU - Alexander, Myriam

AU - Rasheed, Asif

AU - Wormser, David

AU - Soranzo, Nicole

AU - Hammond, Naomi

AU - Butterworth, Adam

AU - Zaidi, Moazzam

AU - Haycock, Philip

AU - Bumpstead, Suzannah

AU - Potter, Simon

AU - Blackburn, Hannah

AU - Gray, Emma

AU - Di Angelantonio, Emanuele

AU - Kaptoge, Stephen

AU - Shah, Nabi

AU - Samuel, Maria

AU - Janjua, Ahmedyar

AU - Sheikh, Nasir

AU - Razi Haider, Shajjia

AU - Murtaza, Muhammed

AU - Ahmad, Usman

AU - Hakeem, Abdul

AU - Ali Memon, Muhammad

AU - Hayat Mallick, Nadeem

AU - Azhar, Muhammad

AU - Samad, Abdus

AU - Rasheed, Syed Zahed

AU - Gardezi, Ali Raza

AU - Memon, Nazir Ahmed

AU - Ghaffar, Abdul

AU - Memon, Fazal Ur Rehman

AU - Zaman, Khan Shah

AU - Kundi, Assadullah

AU - Yaqoob, Zia

AU - Ali Cheema, Liaquat

AU - Qamar, Nadeem

AU - Faruqui, Azhar

AU - Jooma, Rashid

AU - Niazi, Jawaid Hassan

AU - Hussain, Mustafa

AU - Kumar, Kishore

AU - Saleem, Asim

AU - Kumar, Kishwar

AU - Salman Daood, Muhammad

AU - Memon, Fatima

AU - Alam Gul, Aftab

AU - Abbas, Shahid

AU - Zafar, Junaid

AU - Shahid, Faisal

AU - Memon, Zehra

AU - Majeed Bhatti, Shahzad

AU - Kayani, Waleed

AU - Saadat Ali, Syed

AU - Fahim, Muhammad

AU - Ishaq, Muhammad

AU - Frossard, Philippe

AU - Deloukas, Panos

AU - Danesh, John

PY - 2010/7

Y1 - 2010/7

N2 - Objective-: To examine variants at the 9p21 locus in a case-control study of acute myocardial infarction (MI) in Pakistanis and to perform an updated meta-analysis of published studies in people of European ancestry. Methods and Results-: A total of 1851 patients with first-ever confirmed MI and 1903 controls were genotyped for 89 tagging single-nucleotide polymorphisms at locus 9p21, including the lead variant (rs1333049) identified by the Wellcome Trust Case Control Consortium. Minor allele frequencies and extent of linkage disequilibrium observed in Pakistanis were broadly similar to those seen in Europeans. In the Pakistani study, 6 variants were associated with MI (P<10-2) in the initial sample set, and in an additional 741 cases and 674 controls in whom further genotyping was performed for these variants. For Pakistanis, the odds ratio for MI was 1.13 (95% CI, 1.05 to 1.22; P=2×10-3) for each copy of the C allele at rs1333049. In comparison, a meta-analysis of studies in Europeans yielded an odds ratio of 1.31 (95% CI, 1.26 to 1.37) for the same variant (P=1×10-3 for heterogeneity). Meta-analyses of 23 variants, in up to 38 250 cases and 84 820 controls generally yielded higher values in Europeans than in Pakistanis. Conclusion-: To our knowledge, this study provides the first demonstration that variants at the 9p21 locus are significantly associated with MI risk in Pakistanis. However, association signals at this locus were weaker in Pakistanis than those in European studies.

AB - Objective-: To examine variants at the 9p21 locus in a case-control study of acute myocardial infarction (MI) in Pakistanis and to perform an updated meta-analysis of published studies in people of European ancestry. Methods and Results-: A total of 1851 patients with first-ever confirmed MI and 1903 controls were genotyped for 89 tagging single-nucleotide polymorphisms at locus 9p21, including the lead variant (rs1333049) identified by the Wellcome Trust Case Control Consortium. Minor allele frequencies and extent of linkage disequilibrium observed in Pakistanis were broadly similar to those seen in Europeans. In the Pakistani study, 6 variants were associated with MI (P<10-2) in the initial sample set, and in an additional 741 cases and 674 controls in whom further genotyping was performed for these variants. For Pakistanis, the odds ratio for MI was 1.13 (95% CI, 1.05 to 1.22; P=2×10-3) for each copy of the C allele at rs1333049. In comparison, a meta-analysis of studies in Europeans yielded an odds ratio of 1.31 (95% CI, 1.26 to 1.37) for the same variant (P=1×10-3 for heterogeneity). Meta-analyses of 23 variants, in up to 38 250 cases and 84 820 controls generally yielded higher values in Europeans than in Pakistanis. Conclusion-: To our knowledge, this study provides the first demonstration that variants at the 9p21 locus are significantly associated with MI risk in Pakistanis. However, association signals at this locus were weaker in Pakistanis than those in European studies.

KW - 9p21

KW - Pakistanis

KW - South Asia

KW - meta-analysis

KW - myocardial infarction

KW - risk factor

UR - http://www.scopus.com/inward/record.url?scp=77953919563&partnerID=8YFLogxK

U2 - 10.1161/ATVBAHA.109.197210

DO - 10.1161/ATVBAHA.109.197210

M3 - Article

AN - SCOPUS:77953919563

SN - 1079-5642

VL - 30

SP - 1467

EP - 1473

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

IS - 7

ER -

Association of the 9p21.3 locus with risk of first-ever myocardial infarction in pakistanis: Case-control study in south asia and updated meta-analysis of europeans

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Keywords

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