title: Incorporating a Genetic Risk Score Into Coronary Heart Disease Risk Estimates: Effect on Low-Density Lipoprotein Cholesterol Levels (the MI-GENES Clinical Trial).
abstract: BACKGROUND
  Whether knowledge of genetic risk for coronary heart disease (CHD) affects health-related outcomes is unknown. We investigated whether incorporating a genetic risk score (GRS) in CHD risk estimates lowers low-density lipoprotein cholesterol (LDL-C) levels.
  
  
  RESULTS
  Participants (n=203, 45-65 years of age, at intermediate risk for CHD, and not on statins) were randomly assigned to receive their 10-year probability of CHD based either on a conventional risk score (CRS) or CRS + GRS ((+)GRS). Participants in the (+)GRS group were stratified as having high or average/low GRS. Risk was disclosed by a genetic counselor followed by shared decision making regarding statin therapy with a physician. We compared the primary end point of LDL-C levels at 6 months and assessed whether any differences were attributable to changes in dietary fat intake, physical activity levels, or statin use. Participants (mean age, 59.4±5 years; 48% men; mean 10-year CHD risk, 8.5±4.1%) were allocated to receive either CRS (n=100) or (+)GRS (n=103). At the end of the study period, the (+)GRS group had a lower LDL-C than the CRS group (96.5±32.7 versus 105.9±33.3 mg/dL; P=0.04). Participants with high GRS had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants (P=0.02) but not participants with low GRS (100.9±32.2 mg/dL; P=0.18). Statins were initiated more often in the (+)GRS group than in the CRS group (39% versus 22%, P<0.01). No significant differences in dietary fat intake and physical activity levels were noted.
  
  
  CONCLUSIONS
  Disclosure of CHD risk estimates that incorporated genetic risk information led to lower LDL-C levels than disclosure of CHD risk based on conventional risk factors alone.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT01936675.
authors.affiliation: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN (I.J.K., H.J., E.E.A., S.-A.B., T.M.K., I.N.I., R.A.H., T.S.M., K.S.); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (J.E.O., D.J.S., K.R.B.); Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee (U.B.); Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (R.C.G.); and Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN (V.M.M.). Kullo.Iftikhar@mayo.edu.
authors.forename: Iftikhar J
authors.initials: IJ
authors.lastname: Kullo
authors.affiliation: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN (I.J.K., H.J., E.E.A., S.-A.B., T.M.K., I.N.I., R.A.H., T.S.M., K.S.); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (J.E.O., D.J.S., K.R.B.); Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee (U.B.); Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (R.C.G.); and Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN (V.M.M.).
authors.forename: Hayan
authors.initials: H
authors.lastname: Jouni
authors.affiliation: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN (I.J.K., H.J., E.E.A., S.-A.B., T.M.K., I.N.I., R.A.H., T.S.M., K.S.); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (J.E.O., D.J.S., K.R.B.); Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee (U.B.); Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (R.C.G.); and Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN (V.M.M.).
authors.forename: Erin E
authors.initials: EE
authors.lastname: Austin
authors.affiliation: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN (I.J.K., H.J., E.E.A., S.-A.B., T.M.K., I.N.I., R.A.H., T.S.M., K.S.); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (J.E.O., D.J.S., K.R.B.); Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee (U.B.); Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (R.C.G.); and Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN (V.M.M.).
authors.forename: Sherry-Ann
authors.initials: SA
authors.lastname: Brown
authors.affiliation: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN (I.J.K., H.J., E.E.A., S.-A.B., T.M.K., I.N.I., R.A.H., T.S.M., K.S.); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (J.E.O., D.J.S., K.R.B.); Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee (U.B.); Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (R.C.G.); and Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN (V.M.M.).
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Kruisselbrink
authors.affiliation: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN (I.J.K., H.J., E.E.A., S.-A.B., T.M.K., I.N.I., R.A.H., T.S.M., K.S.); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (J.E.O., D.J.S., K.R.B.); Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee (U.B.); Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (R.C.G.); and Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN (V.M.M.).
authors.forename: Iyad N
authors.initials: IN
authors.lastname: Isseh
authors.affiliation: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN (I.J.K., H.J., E.E.A., S.-A.B., T.M.K., I.N.I., R.A.H., T.S.M., K.S.); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (J.E.O., D.J.S., K.R.B.); Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee (U.B.); Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (R.C.G.); and Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN (V.M.M.).
authors.forename: Raad A
authors.initials: RA
authors.lastname: Haddad
authors.affiliation: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN (I.J.K., H.J., E.E.A., S.-A.B., T.M.K., I.N.I., R.A.H., T.S.M., K.S.); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (J.E.O., D.J.S., K.R.B.); Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee (U.B.); Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (R.C.G.); and Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN (V.M.M.).
authors.forename: Tariq S
authors.initials: TS
authors.lastname: Marroush
authors.affiliation: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN (I.J.K., H.J., E.E.A., S.-A.B., T.M.K., I.N.I., R.A.H., T.S.M., K.S.); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (J.E.O., D.J.S., K.R.B.); Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee (U.B.); Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (R.C.G.); and Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN (V.M.M.).
authors.forename: Khader
authors.initials: K
authors.lastname: Shameer
authors.affiliation: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN (I.J.K., H.J., E.E.A., S.-A.B., T.M.K., I.N.I., R.A.H., T.S.M., K.S.); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (J.E.O., D.J.S., K.R.B.); Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee (U.B.); Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (R.C.G.); and Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN (V.M.M.).
authors.forename: Janet E
authors.initials: JE
authors.lastname: Olson
authors.affiliation: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN (I.J.K., H.J., E.E.A., S.-A.B., T.M.K., I.N.I., R.A.H., T.S.M., K.S.); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (J.E.O., D.J.S., K.R.B.); Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee (U.B.); Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (R.C.G.); and Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN (V.M.M.).
authors.forename: Ulrich
authors.initials: U
authors.lastname: Broeckel
authors.affiliation: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN (I.J.K., H.J., E.E.A., S.-A.B., T.M.K., I.N.I., R.A.H., T.S.M., K.S.); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (J.E.O., D.J.S., K.R.B.); Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee (U.B.); Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (R.C.G.); and Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN (V.M.M.).
authors.forename: Robert C
authors.initials: RC
authors.lastname: Green
authors.affiliation: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN (I.J.K., H.J., E.E.A., S.-A.B., T.M.K., I.N.I., R.A.H., T.S.M., K.S.); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (J.E.O., D.J.S., K.R.B.); Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee (U.B.); Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (R.C.G.); and Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN (V.M.M.).
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Schaid
authors.affiliation: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN (I.J.K., H.J., E.E.A., S.-A.B., T.M.K., I.N.I., R.A.H., T.S.M., K.S.); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (J.E.O., D.J.S., K.R.B.); Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee (U.B.); Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (R.C.G.); and Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN (V.M.M.).
authors.forename: Victor M
authors.initials: VM
authors.lastname: Montori
authors.affiliation: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN (I.J.K., H.J., E.E.A., S.-A.B., T.M.K., I.N.I., R.A.H., T.S.M., K.S.); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (J.E.O., D.J.S., K.R.B.); Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee (U.B.); Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (R.C.G.); and Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN (V.M.M.).
authors.forename: Kent R
authors.initials: KR
authors.lastname: Bailey
mesh_terms: D000368:Aged; D001007:Anxiety / Q000453:epidemiology; D008078:Cholesterol, LDL / Q000097:blood*; D015897:Comorbidity; D003327:Coronary Disease / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D003657:Decision Making; D004041:Dietary Fats; D005260:Female; D005500:Follow-Up Studies; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008910:Minnesota / Q000453:epidemiology; D009043:Motor Activity; D010358:Patient Participation; D010817:Physician-Patient Relations; D020641:Polymorphism, Single Nucleotide; D011336:Probability; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D008078:Cholesterol, LDL; D004041:Dietary Fats; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: coronary disease; genetic risk disclosure; genetic risk score; genomics; hydroxymethylglutaryl-CoA reductase inhibitors; polymorphism, single-nucleotide; prevention & control; randomized clinical trials