In the JournalsPerspective

Polygenic risk score predicts early-onset CAD

Patients who presented with early-onset CAD have a significant polygenic contribution that may be more common than familial hypercholesterolemia, according to a study published in Circulation: Genomic and Precision Medicine.

“The increase in genetic risk was independent of other known risk factors, suggesting that testing for multiple genetic differences is clinically useful to evaluate risk and guide management,” Guillaume Paré, MD, MSc, FRCPC, director of the Genetic and Molecular Epidemiology Laboratory and associate professor of medicine at McMaster University and Hamilton Health Sciences in Ontario, Canada, said in a press release. “Combining polygenic screening with current testing for familial hypercholesterolemia could potentially increase fivefold the number of cases for which a genetic explanation can be found.”

Researchers calculated risk for 111,418 participants with (n = 96; 77 men) and without early-onset CAD (n = 111,283; median age, 58 years; 47% men) from the UK Biobank cohort. Participants with early-onset CAD (age 40 or younger for men; age 45 or younger for women) had self-reported angina or MI and documented obstructive CAD.

Data from a local cohort (n = 30; 20 women) also were reviewed, which included participants with significant obstructive CAD. Those with a secondary cause of CAD were excluded.

Genetic risk was calculated with 182 single nucleotide polymorphisms that were associated with CAD.

Participants with early-onset CAD from the UK Biobank cohort had a higher risk score (11.21) compared with the control group (10.88; P = 3.21 x 109). An increase in 1 standard deviation in risk score was associated with an OR of 1.84 (95% CI, 1.52-2.24) for early-onset CAD. This was similar after adjusting for sex, age, smoking, waist-to-hip ratio, diabetes, hypertension and first-degree family history of heart disease (OR = 1.78; 95% CI, 1.45-2.17).

Early-onset CAD risk shown by the occurrence of a polygenic contribution was 1 in 53 in the UK Biobank cohort, which is similar to what was seen in familial hypercholesterolemia.

Participants in the local cohort had a higher risk score (11.23) compared with those in the UK Biobank cohort who did not have early-onset CAD (10.88; P = .001).

Seven patients from the local cohort had a twofold increased risk for early-onset CAD vs. the control group in the UK Biobank cohort. These patients did not have a rare mutation that would cause early-onset CAD or monogenic dyslipidemia.

“This could provide answers to patients affected by such distressing events and would allow genetic screening of relatives,” Paré and colleagues wrote. “Further prospective studies are warranted to confirm the benefits of this approach.” – by Darlene Dobkowski

Disclosures: Paré reports he is supported by the CISCO Professorship in Integrated Health Biosystems. Please see the study for all other authors’ relevant financial disclosures.

 

Patients who presented with early-onset CAD have a significant polygenic contribution that may be more common than familial hypercholesterolemia, according to a study published in Circulation: Genomic and Precision Medicine.

“The increase in genetic risk was independent of other known risk factors, suggesting that testing for multiple genetic differences is clinically useful to evaluate risk and guide management,” Guillaume Paré, MD, MSc, FRCPC, director of the Genetic and Molecular Epidemiology Laboratory and associate professor of medicine at McMaster University and Hamilton Health Sciences in Ontario, Canada, said in a press release. “Combining polygenic screening with current testing for familial hypercholesterolemia could potentially increase fivefold the number of cases for which a genetic explanation can be found.”

Researchers calculated risk for 111,418 participants with (n = 96; 77 men) and without early-onset CAD (n = 111,283; median age, 58 years; 47% men) from the UK Biobank cohort. Participants with early-onset CAD (age 40 or younger for men; age 45 or younger for women) had self-reported angina or MI and documented obstructive CAD.

Data from a local cohort (n = 30; 20 women) also were reviewed, which included participants with significant obstructive CAD. Those with a secondary cause of CAD were excluded.

Genetic risk was calculated with 182 single nucleotide polymorphisms that were associated with CAD.

Participants with early-onset CAD from the UK Biobank cohort had a higher risk score (11.21) compared with the control group (10.88; P = 3.21 x 109). An increase in 1 standard deviation in risk score was associated with an OR of 1.84 (95% CI, 1.52-2.24) for early-onset CAD. This was similar after adjusting for sex, age, smoking, waist-to-hip ratio, diabetes, hypertension and first-degree family history of heart disease (OR = 1.78; 95% CI, 1.45-2.17).

Early-onset CAD risk shown by the occurrence of a polygenic contribution was 1 in 53 in the UK Biobank cohort, which is similar to what was seen in familial hypercholesterolemia.

Participants in the local cohort had a higher risk score (11.23) compared with those in the UK Biobank cohort who did not have early-onset CAD (10.88; P = .001).

Seven patients from the local cohort had a twofold increased risk for early-onset CAD vs. the control group in the UK Biobank cohort. These patients did not have a rare mutation that would cause early-onset CAD or monogenic dyslipidemia.

“This could provide answers to patients affected by such distressing events and would allow genetic screening of relatives,” Paré and colleagues wrote. “Further prospective studies are warranted to confirm the benefits of this approach.” – by Darlene Dobkowski

Disclosures: Paré reports he is supported by the CISCO Professorship in Integrated Health Biosystems. Please see the study for all other authors’ relevant financial disclosures.

 

    Perspective
    Robert Roberts

    Robert Roberts

    This is the first prospective genetic testing in this subgroup population with premature coronary disease. This has clinical application since it shows how one can perform a genetic screening in individuals that are asymptomatic with a family history of heart disease. It also confirms the rule of genetic screening and prevention of CAD. Further research could determine whether premature CAD should all be screened for genetic variants.

    • Robert Roberts, MD, MACC, FRSC, FRCPC
    • Cardiology Today Editorial Board Member University of Arizona College of Medicine-Phoenix

    Disclosures: Roberts reports no relevant financial disclosures.