Lauren M Severance1, Francisco J Contijoch2, Hannah Carter3, Chun C Fan4, Tyler M Seibert5, Anders M Dale6, Elliot R McVeigh7. 1. Department of Bioengineering, UC San Diego, 9500 Gilman Dr. La Jolla, CA, 92093, USA. 2. Department of Bioengineering, UC San Diego, 9500 Gilman Dr. La Jolla, CA, 92093, USA; Department of Radiology, UC San Diego, 9500 Gilman Dr. La Jolla, CA, 92093, USA. 3. Department of Medicine, Medical Genetics Division, UC San Diego, 9500 Gilman Dr. La Jolla, CA, 92093, USA. 4. Healthlytix, 4747 Executive Dr. Suite 820, San Diego, CA, 92121, USA. 5. Department of Radiation Medicine and Applied Science, UC San Diego, 9500 Gilman Dr. La Jolla, CA, 92093, USA. 6. Department of Radiology, UC San Diego, 9500 Gilman Dr. La Jolla, CA, 92093, USA; Department of Cognitive Science, UC San Diego, 9500 Gilman Dr. La Jolla, CA, 92093, USA; Department of Neurosciences, UC San Diego, 9500 Gilman Dr. La Jolla, CA, 92093, USA. 7. Department of Bioengineering, UC San Diego, 9500 Gilman Dr. La Jolla, CA, 92093, USA; Department of Radiology, UC San Diego, 9500 Gilman Dr. La Jolla, CA, 92093, USA; Department of Medicine, Cardiovascular Division, UC San Diego, 9500 Gilman Dr. La Jolla, CA, 92093, USA. Electronic address: emcveigh@ucsd.edu.
Abstract
BACKGROUND: Genetic risk scores (GRSs) have been associated with CHD events and coronary artery calcium (CAC). We sought to evaluate the ability of a GRS to improve CAC as a screening test. METHODS: Using the results of the most recent genome-wide association studies, we calculated a GRS in 6660 individuals from the Multi-Ethnic Study of Atherosclerosis and used it to determine the optimal age for an individual to undergo CAC screening. RESULTS: This 157-SNP GRS was predictive of non-zero CAC in individuals aged 44-54 and improved the positive yield of CAC as a screening test in this age group. The GRS was predictive of CAC in the entire multi-ethnic cohort and in each self-identified ethnic group (European American, Chinese American, African American, and Hispanic American) assessed individually. Given a specified target yield rate of non-zero CAC, an equation was derived to calculate an individual's optimal age to undergo CAC screening. In addition, a "direct-to-consumer" GRS consisting of only risk SNPs or their proxies that are directly genotyped on the 23andMe v5 chip (102-SNP GRS) was assessed in the European American population and was predictive of non-zero CAC in younger individuals. CONCLUSION: A GRS is associated with non-zero CAC in a multi-ethnic cohort and can be used to calculate the age of a person's first calcium scan, given a target threshold for CAC discovery. Furthermore, an inexpensive and widely available "direct-to-consumer" GRS was found to be a viable option to calculate the optimal age for CAC screening.
BACKGROUND: Genetic risk scores (GRSs) have been associated with CHD events and coronary artery calcium (CAC). We sought to evaluate the ability of a GRS to improve CAC as a screening test. METHODS: Using the results of the most recent genome-wide association studies, we calculated a GRS in 6660 individuals from the Multi-Ethnic Study of Atherosclerosis and used it to determine the optimal age for an individual to undergo CAC screening. RESULTS: This 157-SNP GRS was predictive of non-zero CAC in individuals aged 44-54 and improved the positive yield of CAC as a screening test in this age group. The GRS was predictive of CAC in the entire multi-ethnic cohort and in each self-identified ethnic group (European American, Chinese American, African American, and Hispanic American) assessed individually. Given a specified target yield rate of non-zero CAC, an equation was derived to calculate an individual's optimal age to undergo CAC screening. In addition, a "direct-to-consumer" GRS consisting of only risk SNPs or their proxies that are directly genotyped on the 23andMe v5 chip (102-SNP GRS) was assessed in the European American population and was predictive of non-zero CAC in younger individuals. CONCLUSION: A GRS is associated with non-zero CAC in a multi-ethnic cohort and can be used to calculate the age of a person's first calcium scan, given a target threshold for CAC discovery. Furthermore, an inexpensive and widely available "direct-to-consumer" GRS was found to be a viable option to calculate the optimal age for CAC screening.
Authors: Robert W Davies; Sonny Dandona; Alexandre F R Stewart; Li Chen; Stephan G Ellis; W H Wilson Tang; Stanley L Hazen; Robert Roberts; Ruth McPherson; George A Wells Journal: Circ Cardiovasc Genet Date: 2010-08-21
Authors: Peter W F Wilson; Tamar S Polonsky; Michael D Miedema; Amit Khera; Andrzej S Kosinski; Jeffrey T Kuvin Journal: Circulation Date: 2018-11-10 Impact factor: 29.690
Authors: Ruth McPherson; Alexander Pertsemlidis; Nihan Kavaslar; Alexandre Stewart; Robert Roberts; David R Cox; David A Hinds; Len A Pennacchio; Anne Tybjaerg-Hansen; Aaron R Folsom; Eric Boerwinkle; Helen H Hobbs; Jonathan C Cohen Journal: Science Date: 2007-05-03 Impact factor: 47.728
Authors: Joseph Yeboah; Robyn L McClelland; Tamar S Polonsky; Gregory L Burke; Christopher T Sibley; Daniel O'Leary; Jeffery J Carr; David C Goff; Philip Greenland; David M Herrington Journal: JAMA Date: 2012-08-22 Impact factor: 56.272
Authors: Khurram Nasir; Marcio S Bittencourt; Michael J Blaha; Ron Blankstein; Arthur S Agatson; Juan J Rivera; Michael D Miedema; Michael D Miemdema; Christopher T Sibley; Leslee J Shaw; Roger S Blumenthal; Matthew J Budoff; Harlan M Krumholz Journal: J Am Coll Cardiol Date: 2015-10-13 Impact factor: 24.094
Authors: Amit V Khera; Connor A Emdin; Isabel Drake; Pradeep Natarajan; Alexander G Bick; Nancy R Cook; Daniel I Chasman; Usman Baber; Roxana Mehran; Daniel J Rader; Valentin Fuster; Eric Boerwinkle; Olle Melander; Marju Orho-Melander; Paul M Ridker; Sekar Kathiresan Journal: N Engl J Med Date: 2016-11-13 Impact factor: 91.245
Authors: Joanna M M Howson; Wei Zhao; Daniel R Barnes; Weang-Kee Ho; Robin Young; Dirk S Paul; Lindsay L Waite; Daniel F Freitag; Eric B Fauman; Elias L Salfati; Benjamin B Sun; John D Eicher; Andrew D Johnson; Wayne H H Sheu; Sune F Nielsen; Wei-Yu Lin; Praveen Surendran; Anders Malarstig; Jemma B Wilk; Anne Tybjærg-Hansen; Katrine L Rasmussen; Pia R Kamstrup; Panos Deloukas; Jeanette Erdmann; Sekar Kathiresan; Nilesh J Samani; Heribert Schunkert; Hugh Watkins; Ron Do; Daniel J Rader; Julie A Johnson; Stanley L Hazen; Arshed A Quyyumi; John A Spertus; Carl J Pepine; Nora Franceschini; Anne Justice; Alex P Reiner; Steven Buyske; Lucia A Hindorff; Cara L Carty; Kari E North; Charles Kooperberg; Eric Boerwinkle; Kristin Young; Mariaelisa Graff; Ulrike Peters; Devin Absher; Chao A Hsiung; Wen-Jane Lee; Kent D Taylor; Ying-Hsiang Chen; I-Te Lee; Xiuqing Guo; Ren-Hua Chung; Yi-Jen Hung; Jerome I Rotter; Jyh-Ming J Juang; Thomas Quertermous; Tzung-Dau Wang; Asif Rasheed; Philippe Frossard; Dewan S Alam; Abdulla Al Shafi Majumder; Emanuele Di Angelantonio; Rajiv Chowdhury; Yii-Der Ida Chen; Børge G Nordestgaard; Themistocles L Assimes; John Danesh; Adam S Butterworth; Danish Saleheen Journal: Nat Genet Date: 2017-05-22 Impact factor: 41.307
Authors: Nilesh J Samani; Jeanette Erdmann; Alistair S Hall; Christian Hengstenberg; Massimo Mangino; Bjoern Mayer; Richard J Dixon; Thomas Meitinger; Peter Braund; H-Erich Wichmann; Jennifer H Barrett; Inke R König; Suzanne E Stevens; Silke Szymczak; David-Alexandre Tregouet; Mark M Iles; Friedrich Pahlke; Helen Pollard; Wolfgang Lieb; Francois Cambien; Marcus Fischer; Willem Ouwehand; Stefan Blankenberg; Anthony J Balmforth; Andrea Baessler; Stephen G Ball; Tim M Strom; Ingrid Braenne; Christian Gieger; Panos Deloukas; Martin D Tobin; Andreas Ziegler; John R Thompson; Heribert Schunkert Journal: N Engl J Med Date: 2007-07-18 Impact factor: 91.245
Authors: Quinn S Wells; Minoo Bagheri; Aaron W Aday; Deepak K Gupta; Christian M Shaffer; Wei-Qi Wei; Nataraja Sarna Vaitinadin; Sadiya S Khan; Philip Greenland; Thomas J Wang; C Michael Stein; Dan M Roden; Jonathan D Mosley Journal: Circ Genom Precis Med Date: 2021-08-31