Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction

Christopher J. Odonnell, Maryam Kavousi, Albert V. Smith, Sharon L R Kardia, Mary F. Feitosa, Shih Jen Hwang, Yan V. Sun, Michael A. Province, Thor Aspelund, Abbas Dehghan, Udo Hoffmann, Lawrence F. Bielak, Qunyuan Zhang, Gudny Eiriksdottir, Cornelia M. Van Duijn, Caroline S. Fox, Mariza De Andrade, Aldi T. Kraja, Sigurdur Sigurdsson, Suzette E. Elias-Smale & 47 others Joanne M. Murabito, Lenore J. Launer, Aad Van Der Lugt, Sekar Kathiresan, Gabriel P. Krestin, David M. Herrington, Timothy D. Howard, Yongmei Liu, Wendy S Post, Braxton D. Mitchell, Jeffrey R. Oconnell, Haiqing Shen, Alan R. Shuldiner, David Altshuler, Roberto Elosua, Veikko Salomaa, Stephen M. Schwartz, David S. Siscovick, Benjamin F. Voight, Joshua C. Bis, Nicole L. Glazer, Bruce M. Psaty, Eric Boerwinkle, Gerardo Heiss, Stefan Blankenberg, Tanja Zeller, Philipp S. Wild, Renate B. Schnabel, Arne Schillert, Andreas Ziegler, Thomas F. Münzel, Charles C. White, Jerome I. Rotter, Michael Nalls, Matthijs Oudkerk, Andrew D. Johnson, Anne B. Newman, Andre G. Uitterlinden, Joseph M. Massaro, Julie Cunningham, Tamara B. Harris, Albert Hofman, Patricia A. Peyser, Ingrid B. Borecki, L. Adrienne Cupples, Vilmundur Gudnason, Jacqueline C M Witteman

Research output: Contribution to journalArticle

Abstract

BACKGROUND-: Coronary artery calcification (CAC) detected by computed tomography is a noninvasive measure of coronary atherosclerosis, which underlies most cases of myocardial infarction (MI). We sought to identify common genetic variants associated with CAC and further investigate their associations with MI. METHODS AND RESULTS-: Computed tomography was used to assess quantity of CAC. A meta-analysis of genome-wide association studies for CAC was performed in 9961 men and women from 5 independent community-based cohorts, with replication in 3 additional independent cohorts (n=6032). We examined the top single-nucleotide polymorphisms (SNPs) associated with CAC quantity for association with MI in multiple large genome-wide association studies of MI. Genome-wide significant associations with CAC for SNPs on chromosome 9p21 near CDKN2A and CDKN2B (top SNP: rs1333049; P=7.58×10) and 6p24 (top SNP: rs9349379, within the PHACTR1 gene; P=2.65×10) replicated for CAC and for MI. Additionally, there is evidence for concordance of SNP associations with both CAC and MI at a number of other loci, including 3q22 (MRAS gene), 13q34 (COL4A1/COL4A2 genes), and 1p13 (SORT1 gene). CONCLUSIONS-: SNPs in the 9p21 and PHACTR1 gene loci were strongly associated with CAC and MI, and there are suggestive associations with both CAC and MI of SNPs in additional loci. Multiple genetic loci are associated with development of both underlying coronary atherosclerosis and clinical events.

Original languageEnglish (US)
Pages (from-to)2855-2864
Number of pages10
JournalCirculation
Volume124
Issue number25
DOIs
StatePublished - Dec 20 2011
Externally publishedYes

Fingerprint

Genome-Wide Association Study
Coronary Vessels
Myocardial Infarction
Single Nucleotide Polymorphism
Genes
Coronary Artery Disease
Tomography
Genetic Loci
Meta-Analysis
Chromosomes
Genome

Keywords

  • Cardiac computed tomography
  • Coronary artery calcification
  • Coronary atherosclerosis
  • Genome-wide association studies
  • Myocardial infarction

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Odonnell, C. J., Kavousi, M., Smith, A. V., Kardia, S. L. R., Feitosa, M. F., Hwang, S. J., ... Witteman, J. C. M. (2011). Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction. Circulation, 124(25), 2855-2864. https://doi.org/10.1161/CIRCULATIONAHA.110.974899

Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction. / Odonnell, Christopher J.; Kavousi, Maryam; Smith, Albert V.; Kardia, Sharon L R; Feitosa, Mary F.; Hwang, Shih Jen; Sun, Yan V.; Province, Michael A.; Aspelund, Thor; Dehghan, Abbas; Hoffmann, Udo; Bielak, Lawrence F.; Zhang, Qunyuan; Eiriksdottir, Gudny; Van Duijn, Cornelia M.; Fox, Caroline S.; De Andrade, Mariza; Kraja, Aldi T.; Sigurdsson, Sigurdur; Elias-Smale, Suzette E.; Murabito, Joanne M.; Launer, Lenore J.; Van Der Lugt, Aad; Kathiresan, Sekar; Krestin, Gabriel P.; Herrington, David M.; Howard, Timothy D.; Liu, Yongmei; Post, Wendy S; Mitchell, Braxton D.; Oconnell, Jeffrey R.; Shen, Haiqing; Shuldiner, Alan R.; Altshuler, David; Elosua, Roberto; Salomaa, Veikko; Schwartz, Stephen M.; Siscovick, David S.; Voight, Benjamin F.; Bis, Joshua C.; Glazer, Nicole L.; Psaty, Bruce M.; Boerwinkle, Eric; Heiss, Gerardo; Blankenberg, Stefan; Zeller, Tanja; Wild, Philipp S.; Schnabel, Renate B.; Schillert, Arne; Ziegler, Andreas; Münzel, Thomas F.; White, Charles C.; Rotter, Jerome I.; Nalls, Michael; Oudkerk, Matthijs; Johnson, Andrew D.; Newman, Anne B.; Uitterlinden, Andre G.; Massaro, Joseph M.; Cunningham, Julie; Harris, Tamara B.; Hofman, Albert; Peyser, Patricia A.; Borecki, Ingrid B.; Cupples, L. Adrienne; Gudnason, Vilmundur; Witteman, Jacqueline C M.

In: Circulation, Vol. 124, No. 25, 20.12.2011, p. 2855-2864.

Research output: Contribution to journalArticle

Odonnell, CJ, Kavousi, M, Smith, AV, Kardia, SLR, Feitosa, MF, Hwang, SJ, Sun, YV, Province, MA, Aspelund, T, Dehghan, A, Hoffmann, U, Bielak, LF, Zhang, Q, Eiriksdottir, G, Van Duijn, CM, Fox, CS, De Andrade, M, Kraja, AT, Sigurdsson, S, Elias-Smale, SE, Murabito, JM, Launer, LJ, Van Der Lugt, A, Kathiresan, S, Krestin, GP, Herrington, DM, Howard, TD, Liu, Y, Post, WS, Mitchell, BD, Oconnell, JR, Shen, H, Shuldiner, AR, Altshuler, D, Elosua, R, Salomaa, V, Schwartz, SM, Siscovick, DS, Voight, BF, Bis, JC, Glazer, NL, Psaty, BM, Boerwinkle, E, Heiss, G, Blankenberg, S, Zeller, T, Wild, PS, Schnabel, RB, Schillert, A, Ziegler, A, Münzel, TF, White, CC, Rotter, JI, Nalls, M, Oudkerk, M, Johnson, AD, Newman, AB, Uitterlinden, AG, Massaro, JM, Cunningham, J, Harris, TB, Hofman, A, Peyser, PA, Borecki, IB, Cupples, LA, Gudnason, V & Witteman, JCM 2011, 'Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction', Circulation, vol. 124, no. 25, pp. 2855-2864. https://doi.org/10.1161/CIRCULATIONAHA.110.974899
Odonnell CJ, Kavousi M, Smith AV, Kardia SLR, Feitosa MF, Hwang SJ et al. Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction. Circulation. 2011 Dec 20;124(25):2855-2864. https://doi.org/10.1161/CIRCULATIONAHA.110.974899
Odonnell, Christopher J. ; Kavousi, Maryam ; Smith, Albert V. ; Kardia, Sharon L R ; Feitosa, Mary F. ; Hwang, Shih Jen ; Sun, Yan V. ; Province, Michael A. ; Aspelund, Thor ; Dehghan, Abbas ; Hoffmann, Udo ; Bielak, Lawrence F. ; Zhang, Qunyuan ; Eiriksdottir, Gudny ; Van Duijn, Cornelia M. ; Fox, Caroline S. ; De Andrade, Mariza ; Kraja, Aldi T. ; Sigurdsson, Sigurdur ; Elias-Smale, Suzette E. ; Murabito, Joanne M. ; Launer, Lenore J. ; Van Der Lugt, Aad ; Kathiresan, Sekar ; Krestin, Gabriel P. ; Herrington, David M. ; Howard, Timothy D. ; Liu, Yongmei ; Post, Wendy S ; Mitchell, Braxton D. ; Oconnell, Jeffrey R. ; Shen, Haiqing ; Shuldiner, Alan R. ; Altshuler, David ; Elosua, Roberto ; Salomaa, Veikko ; Schwartz, Stephen M. ; Siscovick, David S. ; Voight, Benjamin F. ; Bis, Joshua C. ; Glazer, Nicole L. ; Psaty, Bruce M. ; Boerwinkle, Eric ; Heiss, Gerardo ; Blankenberg, Stefan ; Zeller, Tanja ; Wild, Philipp S. ; Schnabel, Renate B. ; Schillert, Arne ; Ziegler, Andreas ; Münzel, Thomas F. ; White, Charles C. ; Rotter, Jerome I. ; Nalls, Michael ; Oudkerk, Matthijs ; Johnson, Andrew D. ; Newman, Anne B. ; Uitterlinden, Andre G. ; Massaro, Joseph M. ; Cunningham, Julie ; Harris, Tamara B. ; Hofman, Albert ; Peyser, Patricia A. ; Borecki, Ingrid B. ; Cupples, L. Adrienne ; Gudnason, Vilmundur ; Witteman, Jacqueline C M. / Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction. In: Circulation. 2011 ; Vol. 124, No. 25. pp. 2855-2864.
@article{8fd2d8dda25440dba3b8766c7bcda143,
title = "Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction",
abstract = "BACKGROUND-: Coronary artery calcification (CAC) detected by computed tomography is a noninvasive measure of coronary atherosclerosis, which underlies most cases of myocardial infarction (MI). We sought to identify common genetic variants associated with CAC and further investigate their associations with MI. METHODS AND RESULTS-: Computed tomography was used to assess quantity of CAC. A meta-analysis of genome-wide association studies for CAC was performed in 9961 men and women from 5 independent community-based cohorts, with replication in 3 additional independent cohorts (n=6032). We examined the top single-nucleotide polymorphisms (SNPs) associated with CAC quantity for association with MI in multiple large genome-wide association studies of MI. Genome-wide significant associations with CAC for SNPs on chromosome 9p21 near CDKN2A and CDKN2B (top SNP: rs1333049; P=7.58×10) and 6p24 (top SNP: rs9349379, within the PHACTR1 gene; P=2.65×10) replicated for CAC and for MI. Additionally, there is evidence for concordance of SNP associations with both CAC and MI at a number of other loci, including 3q22 (MRAS gene), 13q34 (COL4A1/COL4A2 genes), and 1p13 (SORT1 gene). CONCLUSIONS-: SNPs in the 9p21 and PHACTR1 gene loci were strongly associated with CAC and MI, and there are suggestive associations with both CAC and MI of SNPs in additional loci. Multiple genetic loci are associated with development of both underlying coronary atherosclerosis and clinical events.",
keywords = "Cardiac computed tomography, Coronary artery calcification, Coronary atherosclerosis, Genome-wide association studies, Myocardial infarction",
author = "Odonnell, {Christopher J.} and Maryam Kavousi and Smith, {Albert V.} and Kardia, {Sharon L R} and Feitosa, {Mary F.} and Hwang, {Shih Jen} and Sun, {Yan V.} and Province, {Michael A.} and Thor Aspelund and Abbas Dehghan and Udo Hoffmann and Bielak, {Lawrence F.} and Qunyuan Zhang and Gudny Eiriksdottir and {Van Duijn}, {Cornelia M.} and Fox, {Caroline S.} and {De Andrade}, Mariza and Kraja, {Aldi T.} and Sigurdur Sigurdsson and Elias-Smale, {Suzette E.} and Murabito, {Joanne M.} and Launer, {Lenore J.} and {Van Der Lugt}, Aad and Sekar Kathiresan and Krestin, {Gabriel P.} and Herrington, {David M.} and Howard, {Timothy D.} and Yongmei Liu and Post, {Wendy S} and Mitchell, {Braxton D.} and Oconnell, {Jeffrey R.} and Haiqing Shen and Shuldiner, {Alan R.} and David Altshuler and Roberto Elosua and Veikko Salomaa and Schwartz, {Stephen M.} and Siscovick, {David S.} and Voight, {Benjamin F.} and Bis, {Joshua C.} and Glazer, {Nicole L.} and Psaty, {Bruce M.} and Eric Boerwinkle and Gerardo Heiss and Stefan Blankenberg and Tanja Zeller and Wild, {Philipp S.} and Schnabel, {Renate B.} and Arne Schillert and Andreas Ziegler and M{\"u}nzel, {Thomas F.} and White, {Charles C.} and Rotter, {Jerome I.} and Michael Nalls and Matthijs Oudkerk and Johnson, {Andrew D.} and Newman, {Anne B.} and Uitterlinden, {Andre G.} and Massaro, {Joseph M.} and Julie Cunningham and Harris, {Tamara B.} and Albert Hofman and Peyser, {Patricia A.} and Borecki, {Ingrid B.} and Cupples, {L. Adrienne} and Vilmundur Gudnason and Witteman, {Jacqueline C M}",
year = "2011",
month = "12",
day = "20",
doi = "10.1161/CIRCULATIONAHA.110.974899",
language = "English (US)",
volume = "124",
pages = "2855--2864",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "25",

}

TY - JOUR

T1 - Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction

AU - Odonnell, Christopher J.

AU - Kavousi, Maryam

AU - Smith, Albert V.

AU - Kardia, Sharon L R

AU - Feitosa, Mary F.

AU - Hwang, Shih Jen

AU - Sun, Yan V.

AU - Province, Michael A.

AU - Aspelund, Thor

AU - Dehghan, Abbas

AU - Hoffmann, Udo

AU - Bielak, Lawrence F.

AU - Zhang, Qunyuan

AU - Eiriksdottir, Gudny

AU - Van Duijn, Cornelia M.

AU - Fox, Caroline S.

AU - De Andrade, Mariza

AU - Kraja, Aldi T.

AU - Sigurdsson, Sigurdur

AU - Elias-Smale, Suzette E.

AU - Murabito, Joanne M.

AU - Launer, Lenore J.

AU - Van Der Lugt, Aad

AU - Kathiresan, Sekar

AU - Krestin, Gabriel P.

AU - Herrington, David M.

AU - Howard, Timothy D.

AU - Liu, Yongmei

AU - Post, Wendy S

AU - Mitchell, Braxton D.

AU - Oconnell, Jeffrey R.

AU - Shen, Haiqing

AU - Shuldiner, Alan R.

AU - Altshuler, David

AU - Elosua, Roberto

AU - Salomaa, Veikko

AU - Schwartz, Stephen M.

AU - Siscovick, David S.

AU - Voight, Benjamin F.

AU - Bis, Joshua C.

AU - Glazer, Nicole L.

AU - Psaty, Bruce M.

AU - Boerwinkle, Eric

AU - Heiss, Gerardo

AU - Blankenberg, Stefan

AU - Zeller, Tanja

AU - Wild, Philipp S.

AU - Schnabel, Renate B.

AU - Schillert, Arne

AU - Ziegler, Andreas

AU - Münzel, Thomas F.

AU - White, Charles C.

AU - Rotter, Jerome I.

AU - Nalls, Michael

AU - Oudkerk, Matthijs

AU - Johnson, Andrew D.

AU - Newman, Anne B.

AU - Uitterlinden, Andre G.

AU - Massaro, Joseph M.

AU - Cunningham, Julie

AU - Harris, Tamara B.

AU - Hofman, Albert

AU - Peyser, Patricia A.

AU - Borecki, Ingrid B.

AU - Cupples, L. Adrienne

AU - Gudnason, Vilmundur

AU - Witteman, Jacqueline C M

PY - 2011/12/20

Y1 - 2011/12/20

N2 - BACKGROUND-: Coronary artery calcification (CAC) detected by computed tomography is a noninvasive measure of coronary atherosclerosis, which underlies most cases of myocardial infarction (MI). We sought to identify common genetic variants associated with CAC and further investigate their associations with MI. METHODS AND RESULTS-: Computed tomography was used to assess quantity of CAC. A meta-analysis of genome-wide association studies for CAC was performed in 9961 men and women from 5 independent community-based cohorts, with replication in 3 additional independent cohorts (n=6032). We examined the top single-nucleotide polymorphisms (SNPs) associated with CAC quantity for association with MI in multiple large genome-wide association studies of MI. Genome-wide significant associations with CAC for SNPs on chromosome 9p21 near CDKN2A and CDKN2B (top SNP: rs1333049; P=7.58×10) and 6p24 (top SNP: rs9349379, within the PHACTR1 gene; P=2.65×10) replicated for CAC and for MI. Additionally, there is evidence for concordance of SNP associations with both CAC and MI at a number of other loci, including 3q22 (MRAS gene), 13q34 (COL4A1/COL4A2 genes), and 1p13 (SORT1 gene). CONCLUSIONS-: SNPs in the 9p21 and PHACTR1 gene loci were strongly associated with CAC and MI, and there are suggestive associations with both CAC and MI of SNPs in additional loci. Multiple genetic loci are associated with development of both underlying coronary atherosclerosis and clinical events.

AB - BACKGROUND-: Coronary artery calcification (CAC) detected by computed tomography is a noninvasive measure of coronary atherosclerosis, which underlies most cases of myocardial infarction (MI). We sought to identify common genetic variants associated with CAC and further investigate their associations with MI. METHODS AND RESULTS-: Computed tomography was used to assess quantity of CAC. A meta-analysis of genome-wide association studies for CAC was performed in 9961 men and women from 5 independent community-based cohorts, with replication in 3 additional independent cohorts (n=6032). We examined the top single-nucleotide polymorphisms (SNPs) associated with CAC quantity for association with MI in multiple large genome-wide association studies of MI. Genome-wide significant associations with CAC for SNPs on chromosome 9p21 near CDKN2A and CDKN2B (top SNP: rs1333049; P=7.58×10) and 6p24 (top SNP: rs9349379, within the PHACTR1 gene; P=2.65×10) replicated for CAC and for MI. Additionally, there is evidence for concordance of SNP associations with both CAC and MI at a number of other loci, including 3q22 (MRAS gene), 13q34 (COL4A1/COL4A2 genes), and 1p13 (SORT1 gene). CONCLUSIONS-: SNPs in the 9p21 and PHACTR1 gene loci were strongly associated with CAC and MI, and there are suggestive associations with both CAC and MI of SNPs in additional loci. Multiple genetic loci are associated with development of both underlying coronary atherosclerosis and clinical events.

KW - Cardiac computed tomography

KW - Coronary artery calcification

KW - Coronary atherosclerosis

KW - Genome-wide association studies

KW - Myocardial infarction

UR - http://www.scopus.com/inward/record.url?scp=84155163079&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84155163079&partnerID=8YFLogxK

U2 - 10.1161/CIRCULATIONAHA.110.974899

DO - 10.1161/CIRCULATIONAHA.110.974899

M3 - Article

VL - 124

SP - 2855

EP - 2864

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 25

ER -