A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

de Andrade, Mariza; de Vries, Paul S.; van Zuydam, Natalie R.; Zhang, Weihua; Zhao, Wei; Won, Hong-Hee; Hall, Leanne M.; Nikpay, Majid; Hall, L. M.; Nelson, Christopher P.; Hopewell, Jemma C.; CHopewell, J.; Webb, Thomas R.; MArmasu, S.; Hwang, Shih-Jen; Kim, Yun Kyoung; Kleber, Marcus E.; Lau, King Wai; Goel, Anuj; Lu, Xiangfeng; Lu, Yingchang; Lyytikainen, Leo-Pekka; Mihailov, Evelin; Morrison, Alanna C.; Pervjakova, Natalia; Qu, Liming; Rose, Lynda M.; Salfati, Elias; Willenborg, Christina; Huang, Jianfeng; Hh, Won; Saxena, Richa; Koenig, Inke R.; Scholz, Markus; Kanoni, Stavroula; Smith, Albert V.; Tikkanen, Emmi; Huang, Jie; Uitterlinden, Andre; Auro, Kirsi; Yang, Xueli; Saleheen, Danish; Bjonnes, Andrew; Lm, Hall; Chasman, Daniel I.; Chen, Shufeng; Ford, Ian; Kyriakou, Theodosios; Franceschini, Nora; Gieger, Christian; Lindgren, Cecilia M.; Grace, Christopher; De Andrade, M.; De Vries, P. S.; Han, Bok-Ghee; Gustafsson, Stefan; Van Zuydam, N. R.; Jalilzadeh, Shapour; Kessler, Thorsten; König, Inke R.; Lannfelt, Lars; Lieb, Wolfgang; Armasu, Sebastian M.; Lind, Lars; Lokki, Marja-Liisa; Magnusson, Patrik K.; Mallick, Nadeem H.; Mehra, Narinder; Meitinger, Thomas; Memon, Fazal-Ur-Rehman; Anand, Sonia S.; Morris, Andrew P.; Bertram, Lars; Zeng, Lingyao; Nieminen, Markku S.; MLindgren, C.; Beutner, Frank; Pedersen, Nancy L.; Dedoussis, George; Peters, Annette; Frossard, Philippe; Rallidis, Loukianos S.; Gauguier, Dominique; Rasheed, Asif; Stirrups, Kathleen E.; Goodall, Alison H.; Samuel, Maria; Dehghan, Abbas; Gottesman, Omri; Wouter Jukema, J.; Shah, Svati H.; Sinisalo, Juha; Maerz, Winfried; Trompet, Stella; Hall, Alistair S.; Wang, Laiyuan; Alver, Maris; Haber, Marc; Zaman, Khan S.; EStirrups, K.; Cp, Nelson; Hazen, Stanley L.; Hamsten, Anders; Harris, Tamara B.; Ardissino, Diego; Hengstenberg, Christian; Boerwinkle, Eric; Hofman, Albert; Borecki, Ingrid B.; Ingelsson, Erik; Bottinger, Erwin P.; Iribarren, Carlos; Buring, Julie E.; Jc, Hopewell; Jukema, J. Wouter; Chambers, John C.; Karhunen, Pekka J.; SHall, A.; Kim, Bong-Jo; Collins, Rory; Kooner, Jaspal S.; Kullo, Iftikhar J.; Cupples, L. Adrienne; LHazen, S.; Lehtimaki, Terho; Tr, Webb; Danesh, John; Loos, Ruth J. F.; Melander, Olle; Demuth, Ilja; Metspalu, Andres; Elosua, Roberto; März, Winfried; Epstein, Stephen E.; Palmer, Colin N.; Perola, Markus; Esko, Tonu; Quertermous, Thomas; Feitosa, Mary F.; Rader, Daniel J.; Franco, Oscar H.; Ridker, Paul M.; Franzosi, Maria Grazia; Granger, Christopher B.; Ripatti, Samuli; Gu, Dongfeng; Roberts, Robert; Salomaa, Veikko; Gudnason, Vilmundur; Sanghera, Dharambir K.; Schwartz, Stephen M.; Seedorf, Udo; Stewart, Alexandre F.; Stott, David J.; Thiery, Joachim; Zalloua, Pierre A.; O'Donnell, Christopher J.; Reilly, Muredach P.; Thompson, John R.; Watkins, Hugh; Kathiresan, Sekar; Assimes, Themistocles L.; McPherson, Ruth; Erdmann, Jeanette; Adrienne Cupples, L.; Clarke, Robert; Schunkert, Heribert; Samani, Nilesh J.; Deloukas, Panos; Farrall, Martin

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Wei Zhao
de Andrade et al., 2015

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Nature Research, Nature Genetics, 10(47), p. 1121-1130, 2015

DOI: 10.1038/ng.3396

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@article{de Andrade2015,
  abstract = {Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of [sim]185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) &gt; 0.05) and 2.7 million low-frequency (0.005 &lt; MAF &lt; 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate casual genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.},
  author = {de Andrade, Mariza and de Vries, Paul S. and van Zuydam, Natalie R. and Zhang, Weihua and Zhao, Wei and Won, Hong-Hee and Hall, Leanne M. and Nikpay, Majid and Hall, L. M. and Nelson, Christopher P. and Hopewell, Jemma C. and CHopewell, J. and Webb, Thomas R. and MArmasu, S. and Hwang, Shih-Jen and Kim, Yun Kyoung and Kleber, Marcus E. and Lau, King Wai and Goel, Anuj and Lu, Xiangfeng and Lu, Yingchang and Lyytikainen, Leo-Pekka and Mihailov, Evelin and Morrison, Alanna C. and Pervjakova, Natalia and Qu, Liming and Rose, Lynda M. and Salfati, Elias and Willenborg, Christina and Huang, Jianfeng and Hh, Won and Saxena, Richa and Koenig, Inke R. and Scholz, Markus and Kanoni, Stavroula and Smith, Albert V. and Tikkanen, Emmi and Huang, Jie and Uitterlinden, Andre and Auro, Kirsi and Yang, Xueli and Saleheen, Danish and Bjonnes, Andrew and Lm, Hall and Chasman, Daniel I. and Chen, Shufeng and Ford, Ian and Kyriakou, Theodosios and Franceschini, Nora and Gieger, Christian and Lindgren, Cecilia M. and Grace, Christopher and De Andrade, M. and De Vries, P. S. and Han, Bok-Ghee and Gustafsson, Stefan and Van Zuydam, N. R. and Jalilzadeh, Shapour and Kessler, Thorsten and König, Inke R. and Lannfelt, Lars and Lieb, Wolfgang and Armasu, Sebastian M. and Lind, Lars and Lokki, Marja-Liisa and Magnusson, Patrik K. and Mallick, Nadeem H. and Mehra, Narinder and Meitinger, Thomas and Memon, Fazal-Ur-Rehman and Anand, Sonia S. and Morris, Andrew P. and Bertram, Lars and Zeng, Lingyao and Nieminen, Markku S. and MLindgren, C. and Beutner, Frank and Pedersen, Nancy L. and Dedoussis, George and Peters, Annette and Frossard, Philippe and Rallidis, Loukianos S. and Gauguier, Dominique and Rasheed, Asif and Stirrups, Kathleen E. and Goodall, Alison H. and Samuel, Maria and Dehghan, Abbas and Gottesman, Omri and Wouter Jukema, J. and Shah, Svati H. and Sinisalo, Juha and Maerz, Winfried and Trompet, Stella and Hall, Alistair S. and Wang, Laiyuan and Alver, Maris and Haber, Marc and Zaman, Khan S. and EStirrups, K. and Cp, Nelson and Hazen, Stanley L. and Hamsten, Anders and Harris, Tamara B. and Ardissino, Diego and Hengstenberg, Christian and Boerwinkle, Eric and Hofman, Albert and Borecki, Ingrid B. and Ingelsson, Erik and Bottinger, Erwin P. and Iribarren, Carlos and Buring, Julie E. and Jc, Hopewell and Jukema, J. Wouter and Chambers, John C. and Karhunen, Pekka J. and SHall, A. and Kim, Bong-Jo and Collins, Rory and Kooner, Jaspal S. and Kullo, Iftikhar J. and Cupples, L. Adrienne and LHazen, S. and Lehtimaki, Terho and Tr, Webb and Danesh, John and Loos, Ruth J. F. and Melander, Olle and Demuth, Ilja and Metspalu, Andres and Elosua, Roberto and März, Winfried and Epstein, Stephen E. and Palmer, Colin N. and Perola, Markus and Esko, Tonu and Quertermous, Thomas and Feitosa, Mary F. and Rader, Daniel J. and Franco, Oscar H. and Ridker, Paul M. and Franzosi, Maria Grazia and Granger, Christopher B. and Ripatti, Samuli and Gu, Dongfeng and Roberts, Robert and Salomaa, Veikko and Gudnason, Vilmundur and Sanghera, Dharambir K. and Schwartz, Stephen M. and Seedorf, Udo and Stewart, Alexandre F. and Stott, David J. and Thiery, Joachim and Zalloua, Pierre A. and O'Donnell, Christopher J. and Reilly, Muredach P. and Thompson, John R. and Watkins, Hugh and Kathiresan, Sekar and Assimes, Themistocles L. and McPherson, Ruth and Erdmann, Jeanette and Adrienne Cupples, L. and Clarke, Robert and Schunkert, Heribert and Samani, Nilesh J. and Deloukas, Panos and Farrall, Martin},
  doi = {10.1038/ng.3396},
  journal = {Nature Genetics},
  month = {sep},
  pages = {1121-1130},
  title = {A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease},
  url = {http://www.nature.com/articles/ng.3396.pdf},
  volume = {47},
  year = {2015}
}

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A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Journal article published in 2015 by Mariza de Andrade, Paul S. de Vries, Natalie R. van Zuydam, Weihua Zhang, Wei Zhao

, Hong-Hee Won

, Leanne M. Hall, Majid Nikpay, L. M. Hall, Christopher P. Nelson, Jemma C. Hopewell, J. CHopewell, Thomas R. Webb, S. MArmasu, Shih-Jen Hwang and other authors. Mariza de Andrade, Paul S. de Vries, Natalie R. van Zuydam, Weihua Zhang, Wei Zhao

, Hong-Hee Won

, Leanne M. Hall, Majid Nikpay, L. M. Hall, Christopher P. Nelson, Jemma C. Hopewell, J. CHopewell, Thomas R. Webb, S. MArmasu, Shih-Jen Hwang, Yun Kyoung Kim, Marcus E. Kleber

, King Wai Lau, Anuj Goel

, Xiangfeng Lu, Yingchang Lu, Leo-Pekka Lyytikainen, Evelin Mihailov, Alanna C. Morrison, Natalia Pervjakova, Liming Qu, Lynda M. Rose, Elias Salfati, Christina Willenborg, Jianfeng Huang, Won Hh, Richa Saxena, Inke R. Koenig, Markus Scholz, Stavroula Kanoni, Albert V. Smith

, Emmi Tikkanen, Jie Huang, Andre Uitterlinden, Kirsi Auro, Xueli Yang, Danish Saleheen, Andrew Bjonnes, Hall Lm, Daniel I. Chasman, Shufeng Chen, Ian Ford, Theodosios Kyriakou, Nora Franceschini, Christian Gieger

, Cecilia M. Lindgren, Christopher Grace, M. De Andrade, P. S. De Vries, Bok-Ghee Han, Stefan Gustafsson

, N. R. Van Zuydam, Shapour Jalilzadeh, Thorsten Kessler, Inke R. König, Lars Lannfelt, Wolfgang Lieb, Sebastian M. Armasu, Lars Lind, Marja-Liisa Lokki, Patrik K. Magnusson, Nadeem H. Mallick, Narinder Mehra, Thomas Meitinger, Fazal-Ur-Rehman Memon, Sonia S. Anand, Andrew P. Morris, Lars Bertram, Lingyao Zeng, Markku S. Nieminen, C. MLindgren, Frank Beutner, Nancy L. Pedersen, George Dedoussis, Annette Peters, Philippe Frossard, Loukianos S. Rallidis, Dominique Gauguier, Asif Rasheed, Kathleen E. Stirrups, Alison H. Goodall, Maria Samuel, Abbas Dehghan

, Omri Gottesman, J. Wouter Jukema, Svati H. Shah, Juha Sinisalo, Winfried Maerz, Stella Trompet, Alistair S. Hall, Laiyuan Wang, Maris Alver, Marc Haber

, Khan S. Zaman, K. EStirrups, Nelson Cp, Stanley L. Hazen, Anders Hamsten, Tamara B. Harris, Diego Ardissino, Christian Hengstenberg, Eric Boerwinkle, Albert Hofman, Ingrid B. Borecki, Erik Ingelsson, Erwin P. Bottinger, Carlos Iribarren, Julie E. Buring, Hopewell Jc, J. Wouter Jukema, John C. Chambers, Pekka J. Karhunen, A. SHall, Bong-Jo Kim, Rory Collins, Jaspal S. Kooner, Iftikhar J. Kullo, L. Adrienne Cupples, S. LHazen, Terho Lehtimaki, Webb Tr, John Danesh, Ruth J. F. Loos, Olle Melander, Ilja Demuth, Andres Metspalu, Roberto Elosua, Winfried März, Stephen E. Epstein, Colin N. Palmer

, Markus Perola, Tonu Esko

, Thomas Quertermous, Mary F. Feitosa, Daniel J. Rader, Oscar H. Franco, Paul M. Ridker, Maria Grazia Franzosi, Christopher B. Granger, Samuli Ripatti, Dongfeng Gu, Robert Roberts, Veikko Salomaa, Vilmundur Gudnason, Dharambir K. Sanghera, Stephen M. Schwartz, Udo Seedorf, Alexandre F. Stewart, David J. Stott, Joachim Thiery, Pierre A. Zalloua, Christopher J. O'Donnell, Muredach P. Reilly, John R. Thompson, Hugh Watkins, Sekar Kathiresan, Themistocles L. Assimes, Ruth McPherson, Jeanette Erdmann, L. Adrienne Cupples, Robert Clarke, Heribert Schunkert, Nilesh J. Samani, Panos Deloukas

, Martin Farrall

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Abstract

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of [sim]185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate casual genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.

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A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

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