PURPOSE OF REVIEW: Genome-wide association studies (GWAS) have identified ∼60 loci for coronary artery disease (CAD). Through genetic risk scores (GRSs), investigators are leveraging this genomic information to gain insights on both the fundamental mechanisms driving these associations as well as their utility in improving risk prediction. RECENT FINDINGS: GRSs of CAD track with the earliest atherosclerosis lesions in the coronary including fatty streaks and uncomplicated raised lesions. In multiple cohort studies, they predict incident CAD events independent of all traditional and lifestyle risk factors. The incorporation of SNPs with suggestive but not genome-wide association in GWAS into GRSs often increases the strength of these associations. GRS may also predict recurrent events and identify patients most likely to respond to statins. The effect of the GRS on discrimination metrics remains modest but the minimal degree of improvement needed for clinical utility is unknown. SUMMARY: Most novel loci for CAD identified through GWAS facilitate the formation of coronary atherosclerosis and stratify individuals based on their underlying burden of coronary atherosclerosis. GRSs may one day be routinely used in clinical practice to not only assess the risk of incident events but also to predict who will respond best to established prevention strategies.
PURPOSE OF REVIEW: Genome-wide association studies (GWAS) have identified ∼60 loci for coronary artery disease (CAD). Through genetic risk scores (GRSs), investigators are leveraging this genomic information to gain insights on both the fundamental mechanisms driving these associations as well as their utility in improving risk prediction. RECENT FINDINGS: GRSs of CAD track with the earliest atherosclerosis lesions in the coronary including fatty streaks and uncomplicated raised lesions. In multiple cohort studies, they predict incident CAD events independent of all traditional and lifestyle risk factors. The incorporation of SNPs with suggestive but not genome-wide association in GWAS into GRSs often increases the strength of these associations. GRS may also predict recurrent events and identify patients most likely to respond to statins. The effect of the GRS on discrimination metrics remains modest but the minimal degree of improvement needed for clinical utility is unknown. SUMMARY: Most novel loci for CAD identified through GWAS facilitate the formation of coronary atherosclerosis and stratify individuals based on their underlying burden of coronary atherosclerosis. GRSs may one day be routinely used in clinical practice to not only assess the risk of incident events but also to predict who will respond best to established prevention strategies.
Authors: Els Wauters; Kathryn F Carruthers; Ian Buysschaert; Donald R Dunbar; Gilian Peuteman; Ann Belmans; Andrzej Budaj; Frans Van de Werf; Diether Lambrechts; Keith A A Fox Journal: Eur Heart J Date: 2012-11-15 Impact factor: 29.983
Authors: Panos Deloukas; Stavroula Kanoni; Christina Willenborg; Martin Farrall; Themistocles L Assimes; John R Thompson; Erik Ingelsson; Danish Saleheen; Jeanette Erdmann; Benjamin A Goldstein; Kathleen Stirrups; Inke R König; Jean-Baptiste Cazier; Asa Johansson; Alistair S Hall; Jong-Young Lee; Cristen J Willer; John C Chambers; Tõnu Esko; Lasse Folkersen; Anuj Goel; Elin Grundberg; Aki S Havulinna; Weang K Ho; Jemma C Hopewell; Niclas Eriksson; Marcus E Kleber; Kati Kristiansson; Per Lundmark; Leo-Pekka Lyytikäinen; Suzanne Rafelt; Dmitry Shungin; Rona J Strawbridge; Gudmar Thorleifsson; Emmi Tikkanen; Natalie Van Zuydam; Benjamin F Voight; Lindsay L Waite; Weihua Zhang; Andreas Ziegler; Devin Absher; David Altshuler; Anthony J Balmforth; Inês Barroso; Peter S Braund; Christof Burgdorf; Simone Claudi-Boehm; David Cox; Maria Dimitriou; Ron Do; Alex S F Doney; NourEddine El Mokhtari; Per Eriksson; Krista Fischer; Pierre Fontanillas; Anders Franco-Cereceda; Bruna Gigante; Leif Groop; Stefan Gustafsson; Jörg Hager; Göran Hallmans; Bok-Ghee Han; Sarah E Hunt; Hyun M Kang; Thomas Illig; Thorsten Kessler; Joshua W Knowles; Genovefa Kolovou; Johanna Kuusisto; Claudia Langenberg; Cordelia Langford; Karin Leander; Marja-Liisa Lokki; Anders Lundmark; Mark I McCarthy; Christa Meisinger; Olle Melander; Evelin Mihailov; Seraya Maouche; Andrew D Morris; Martina Müller-Nurasyid; Kjell Nikus; John F Peden; N William Rayner; Asif Rasheed; Silke Rosinger; Diana Rubin; Moritz P Rumpf; Arne Schäfer; Mohan Sivananthan; Ci Song; Alexandre F R Stewart; Sian-Tsung Tan; Gudmundur Thorgeirsson; C Ellen van der Schoot; Peter J Wagner; George A Wells; Philipp S Wild; Tsun-Po Yang; Philippe Amouyel; Dominique Arveiler; Hanneke Basart; Michael Boehnke; Eric Boerwinkle; Paolo Brambilla; Francois Cambien; Adrienne L Cupples; Ulf de Faire; Abbas Dehghan; Patrick Diemert; Stephen E Epstein; Alun Evans; Marco M Ferrario; Jean Ferrières; Dominique Gauguier; Alan S Go; Alison H Goodall; Villi Gudnason; Stanley L Hazen; Hilma Holm; Carlos Iribarren; Yangsoo Jang; Mika Kähönen; Frank Kee; Hyo-Soo Kim; Norman Klopp; Wolfgang Koenig; Wolfgang Kratzer; Kari Kuulasmaa; Markku Laakso; Reijo Laaksonen; Ji-Young Lee; Lars Lind; Willem H Ouwehand; Sarah Parish; Jeong E Park; Nancy L Pedersen; Annette Peters; Thomas Quertermous; Daniel J Rader; Veikko Salomaa; Eric Schadt; Svati H Shah; Juha Sinisalo; Klaus Stark; Kari Stefansson; David-Alexandre Trégouët; Jarmo Virtamo; Lars Wallentin; Nicholas Wareham; Martina E Zimmermann; Markku S Nieminen; Christian Hengstenberg; Manjinder S Sandhu; Tomi Pastinen; Ann-Christine Syvänen; G Kees Hovingh; George Dedoussis; Paul W Franks; Terho Lehtimäki; Andres Metspalu; Pierre A Zalloua; Agneta Siegbahn; Stefan Schreiber; Samuli Ripatti; Stefan S Blankenberg; Markus Perola; Robert Clarke; Bernhard O Boehm; Christopher O'Donnell; Muredach P Reilly; Winfried März; Rory Collins; Sekar Kathiresan; Anders Hamsten; Jaspal S Kooner; Unnur Thorsteinsdottir; John Danesh; Colin N A Palmer; Robert Roberts; Hugh Watkins; Heribert Schunkert; Nilesh J Samani Journal: Nat Genet Date: 2012-12-02 Impact factor: 38.330
Authors: J L Mega; N O Stitziel; S Kathiresan; M S Sabatine; J G Smith; D I Chasman; M Caulfield; J J Devlin; F Nordio; C Hyde; C P Cannon; F Sacks; N Poulter; P Sever; P M Ridker; E Braunwald; O Melander Journal: Lancet Date: 2015-03-04 Impact factor: 79.321
Authors: Majid Nikpay; Anuj Goel; Hong-Hee Won; Leanne M Hall; Christina Willenborg; Stavroula Kanoni; Danish Saleheen; Theodosios Kyriakou; Christopher P Nelson; Jemma C Hopewell; Thomas R Webb; Lingyao Zeng; Abbas Dehghan; Maris Alver; Sebastian M Armasu; Kirsi Auro; Andrew Bjonnes; Daniel I Chasman; Shufeng Chen; Ian Ford; Nora Franceschini; Christian Gieger; Christopher Grace; Stefan Gustafsson; Jie Huang; Shih-Jen Hwang; Yun Kyoung Kim; Marcus E Kleber; King Wai Lau; Xiangfeng Lu; Yingchang Lu; Leo-Pekka Lyytikäinen; Evelin Mihailov; Alanna C Morrison; Natalia Pervjakova; Liming Qu; Lynda M Rose; Elias Salfati; Richa Saxena; Markus Scholz; Albert V Smith; Emmi Tikkanen; Andre Uitterlinden; Xueli Yang; Weihua Zhang; Wei Zhao; Mariza de Andrade; Paul S de Vries; Natalie R van Zuydam; Sonia S Anand; Lars Bertram; Frank Beutner; George Dedoussis; Philippe Frossard; Dominique Gauguier; Alison H Goodall; Omri Gottesman; Marc Haber; Bok-Ghee Han; Jianfeng Huang; Shapour Jalilzadeh; Thorsten Kessler; Inke R König; Lars Lannfelt; Wolfgang Lieb; Lars Lind; Cecilia M Lindgren; Marja-Liisa Lokki; Patrik K Magnusson; Nadeem H Mallick; Narinder Mehra; Thomas Meitinger; Fazal-Ur-Rehman Memon; Andrew P Morris; Markku S Nieminen; Nancy L Pedersen; Annette Peters; Loukianos S Rallidis; Asif Rasheed; Maria Samuel; Svati H Shah; Juha Sinisalo; Kathleen E Stirrups; Stella Trompet; Laiyuan Wang; Khan S Zaman; Diego Ardissino; Eric Boerwinkle; Ingrid B Borecki; Erwin P Bottinger; Julie E Buring; John C Chambers; Rory Collins; L Adrienne Cupples; John Danesh; Ilja Demuth; Roberto Elosua; Stephen E Epstein; Tõnu Esko; Mary F Feitosa; Oscar H Franco; Maria Grazia Franzosi; Christopher B Granger; Dongfeng Gu; Vilmundur Gudnason; Alistair S Hall; Anders Hamsten; Tamara B Harris; Stanley L Hazen; Christian Hengstenberg; Albert Hofman; Erik Ingelsson; Carlos Iribarren; J Wouter Jukema; Pekka J Karhunen; Bong-Jo Kim; Jaspal S Kooner; Iftikhar J Kullo; Terho Lehtimäki; Ruth J F Loos; Olle Melander; Andres Metspalu; Winfried März; Colin N Palmer; Markus Perola; Thomas Quertermous; Daniel J Rader; Paul M Ridker; Samuli Ripatti; Robert Roberts; Veikko Salomaa; 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; Themistocles L Assimes; John R Thompson; Jeanette Erdmann; Robert Clarke; Hugh Watkins; Sekar Kathiresan; Ruth McPherson; Panos Deloukas; Heribert Schunkert; Nilesh J Samani; Martin Farrall Journal: Nat Genet Date: 2015-09-07 Impact factor: 38.330
Authors: Christopher S Carlson; Tara C Matise; Kari E North; Christopher A Haiman; Megan D Fesinmeyer; Steven Buyske; Fredrick R Schumacher; Ulrike Peters; Nora Franceschini; Marylyn D Ritchie; David J Duggan; Kylee L Spencer; Logan Dumitrescu; Charles B Eaton; Fridtjof Thomas; Alicia Young; Cara Carty; Gerardo Heiss; Loic Le Marchand; Dana C Crawford; Lucia A Hindorff; Charles L Kooperberg Journal: PLoS Biol Date: 2013-09-17 Impact factor: 8.029
Authors: Mario Luca Morieri; He Gao; Marie Pigeyre; Hetal S Shah; Jennifer Sjaarda; Christine Mendonca; Timothy Hastings; Patinut Buranasupkajorn; Alison A Motsinger-Reif; Daniel M Rotroff; Ronald J Sigal; Santica M Marcovina; Peter Kraft; John B Buse; Michael J Wagner; Hertzel C Gerstein; Josyf C Mychaleckyj; Guillaume Parè; Alessandro Doria Journal: Diabetes Care Date: 2018-09-27 Impact factor: 19.112
Authors: Dana C Crawford; Nicole A Restrepo; Kirsten E Diggins; Eric Farber-Eger; Quinn S Wells Journal: BMC Med Genomics Date: 2018-09-14 Impact factor: 3.063