Quinn S Wells1,2,3, Minoo Bagheri1, Aaron W Aday1, Deepak K Gupta1, Christian M Shaffer1, Wei-Qi Wei1,2, Nataraja Sarna Vaitinadin1, Sadiya S Khan4,5, Philip Greenland4, Thomas J Wang6, C Michael Stein1,3, Dan M Roden1,2,3, Jonathan D Mosley1,2. 1. Department of Medicine (Q.S.W., M.B., A.W.A., D.K.G., C.M. Shaffer, W.-Q.W., N.S.V., C.M. Stein, D.M.R., J.D.M.), Vanderbilt University Medical Center. 2. Department of Biomedical Informatics (Q.S.W., W.Q.W., D.M.R., J.D.M.), Vanderbilt University Medical Center. 3. Department of Pharmacology, Vanderbilt University, Nashville, TN (Q.S.W., C.M. Stein, D.M.R.). 4. Department of Preventive Medicine (S.S.K., P.G.), Northwestern University Feinberg School of Medicine, Chicago, IL. 5. Division of Cardiology, Department of Medicine (S.S.K.), Northwestern University Feinberg School of Medicine, Chicago, IL. 6. Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX (T.J.W.).
Abstract
BACKGROUND: Polygenic risk scores (PRS) may enhance risk stratification for coronary heart disease among young adults. Whether a coronary heart disease PRS improves prediction beyond modifiable risk factors in this population is not known. METHODS: Genotyped adults aged 18 to 35 years were selected from the CARDIA study (Coronary Artery Risk Development in Young Adults; n=1132) and FOS (Framingham Offspring Study; n=663). Systolic blood pressure, total and HDL (high-density lipoprotein) cholesterol, triglycerides, smoking, and waist circumference or body mass index were measured at the visit 1 exam of each study, and coronary artery calcium, a measure of coronary atherosclerosis, was assessed at year 15 (CARDIA) or year 30 (FOS). A previously validated PRS for coronary heart disease was computed for each subject. The C statistic and integrated discrimination improvement were used to compare improvements in prediction of elevated coronary artery calcium between models containing the PRS, risk factors, or both. RESULTS: There were 62 (5%) and 93 (14%) participants with a coronary artery calcium score >20 (CARDIA) and >300 (FOS), respectively. At these thresholds, the C statistic changes of adding the PRS to a risk factor-based model were 0.015 (0.004-0.028) and 0.020 (0.001-0.039) in CARDIA and FOS, respectively. When adding risk factors to a PRS-based model, the respective changes were 0.070 (0.033-0.109) and 0.051 (0.017-0.079). The integrated discrimination improvement, when adding the PRS to a risk factor model, was 0.027 (-0.006 to 0.054) in CARDIA and 0.039 (0.0005-0.072) in FOS. CONCLUSIONS: Among young adults, a PRS improved model discrimination for coronary atherosclerosis, but improvements were smaller than those associated with modifiable risk factors.
BACKGROUND: Polygenic risk scores (PRS) may enhance risk stratification for coronary heart disease among young adults. Whether a coronary heart disease PRS improves prediction beyond modifiable risk factors in this population is not known. METHODS: Genotyped adults aged 18 to 35 years were selected from the CARDIA study (Coronary Artery Risk Development in Young Adults; n=1132) and FOS (Framingham Offspring Study; n=663). Systolic blood pressure, total and HDL (high-density lipoprotein) cholesterol, triglycerides, smoking, and waist circumference or body mass index were measured at the visit 1 exam of each study, and coronary artery calcium, a measure of coronary atherosclerosis, was assessed at year 15 (CARDIA) or year 30 (FOS). A previously validated PRS for coronary heart disease was computed for each subject. The C statistic and integrated discrimination improvement were used to compare improvements in prediction of elevated coronary artery calcium between models containing the PRS, risk factors, or both. RESULTS: There were 62 (5%) and 93 (14%) participants with a coronary artery calcium score >20 (CARDIA) and >300 (FOS), respectively. At these thresholds, the C statistic changes of adding the PRS to a risk factor-based model were 0.015 (0.004-0.028) and 0.020 (0.001-0.039) in CARDIA and FOS, respectively. When adding risk factors to a PRS-based model, the respective changes were 0.070 (0.033-0.109) and 0.051 (0.017-0.079). The integrated discrimination improvement, when adding the PRS to a risk factor model, was 0.027 (-0.006 to 0.054) in CARDIA and 0.039 (0.0005-0.072) in FOS. CONCLUSIONS: Among young adults, a PRS improved model discrimination for coronary atherosclerosis, but improvements were smaller than those associated with modifiable risk factors.
Authors: Emelia J Benjamin; Paul Muntner; Alvaro Alonso; Marcio S Bittencourt; Clifton W Callaway; April P Carson; Alanna M Chamberlain; Alexander R Chang; Susan Cheng; Sandeep R Das; Francesca N Delling; Luc Djousse; Mitchell S V Elkind; Jane F Ferguson; Myriam Fornage; Lori Chaffin Jordan; Sadiya S Khan; Brett M Kissela; Kristen L Knutson; Tak W Kwan; Daniel T Lackland; Tené T Lewis; Judith H Lichtman; Chris T Longenecker; Matthew Shane Loop; Pamela L Lutsey; Seth S Martin; Kunihiro Matsushita; Andrew E Moran; Michael E Mussolino; Martin O'Flaherty; Ambarish Pandey; Amanda M Perak; Wayne D Rosamond; Gregory A Roth; Uchechukwu K A Sampson; Gary M Satou; Emily B Schroeder; Svati H Shah; Nicole L Spartano; Andrew Stokes; David L Tirschwell; Connie W Tsao; Mintu P Turakhia; Lisa B VanWagner; John T Wilkins; Sally S Wong; Salim S Virani Journal: Circulation Date: 2019-03-05 Impact factor: 29.690
Authors: Michael Poon; John R Lesser; Cathleen Biga; Ron Blankstein; Christopher M Kramer; James K Min; Pamela S Noack; Christina Farrow; Udo Hoffman; Jaime Murillo; Koen Nieman; Leslee J Shaw Journal: J Am Coll Cardiol Date: 2020-09-15 Impact factor: 24.094
Authors: Robert Detrano; Alan D Guerci; J Jeffrey Carr; Diane E Bild; Gregory Burke; Aaron R Folsom; Kiang Liu; Steven Shea; Moyses Szklo; David A Bluemke; Daniel H O'Leary; Russell Tracy; Karol Watson; Nathan D Wong; Richard A Kronmal Journal: N Engl J Med Date: 2008-03-27 Impact factor: 91.245
Authors: Catherine M Loria; Kiang Liu; Cora E Lewis; Stephen B Hulley; Stephen Sidney; Pamela J Schreiner; O Dale Williams; Diane E Bild; Robert Detrano Journal: J Am Coll Cardiol Date: 2007-05-04 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: Sadiya S Khan; Courtney Page; Daniel M Wojdyla; Yosef Y Schwartz; Philip Greenland; Michael J Pencina Journal: Circulation Date: 2022-07-26 Impact factor: 39.918