A cross-sectional analysis suggested that a multivariable model of clinical and genetic risk factors explains only 36% of the likelihood of family history of heart disease (FHHD), with most of the risk of a FHHD unexplained. The analysis included 166,714 UK Biobank participants with 43.2% reported a FHHD. In the multivariable model, polygenic risk score for coronary artery disease (PRSCAD, OR 1.30), and heterozygous familial hypercholesterolemia (HeFH, OR 1.31) were most strongly associated with FHHD, followed by clinical risk factors: hypertension (OR 1.18), lipoprotein(a) (OR 1.17), apolipoprotein B-to-apolipoprotein A1 ratio, (OR 1.13) and triglycerides (OR 1.07). Population attributable risks analyses showed that 21.9% of the risk of reporting a FHHD is attributed to clinical factors, 22.2% is attributed to genetic factors, and 36.0% is attributed to genetic and clinical factors combined. The findings suggest that much of the self-reported FHHD is not explained by currently available genetic and clinical biomarkers and implies knowledge gap. Source: https://academic.oup.com/
