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What is the mechanism of genetic contributions to the development of atherosclerosis?

      Cardiovascular disease is a heritable trait, and the heritable factors involved are quite numerous [
      • Khera A.V.
      • Kathiresan S.
      Genetics of coronary artery disease: discovery, biology and clinical translation.
      ]. In fact, physicians routinely collect family history information about cardiovascular disease that has been associated with later events [
      • Yeboah J.
      • McClelland R.L.
      • Polonsky T.S.
      • Burke G.L.
      • Sibley C.T.
      • O'Leary D.
      • et al.
      Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals.
      ]. Family history information is quite useful and can be collected within a few minutes in a noninvasive manner. In addition to this contemporary assessment, recent studies have revealed that a “polygenic risk score,” which reflects a set of common genetic variations, is a useful clinical tool for risk assessment of the development of atherosclerosis [
      • Tada H.
      • Melander O.
      • Louie J.Z.
      • Catanese J.J.
      • Rowland C.M.
      • Devlin J.J.
      • et al.
      Risk prediction by genetic risk scores for coronary heart disease is independent of self-reported family history.
      ,
      • Khera A.V.
      • Chaffin M.
      • Aragam K.G.
      • Haas M.E.
      • Roselli C.
      • Choi S.H.
      • et al.
      Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations.
      ]. Currently, the common genetic variations of coronary atherosclerosis that make up this score appear to be more consequential than those of familial hypercholesterolemia (FH), which has been considered the most frequent and important cause of this extreme situation [
      • Khera A.V.
      • Chaffin M.
      • Zekavat S.M.
      • Collins R.L.
      • Roselli C.
      • Natarajan P.
      • et al.
      Whole-genome sequencing to characterize monogenic and polygenic contributions in patients hospitalized with early-onset myocardial infarction.
      ]. Patients with FH who are at high risk for coronary atherosclerosis are easily identified by an extremely elevated low-density lipoprotein (LDL) cholesterol level; by physical signs, including Achilles tendon thickness; and family history information. On the other hand, with the conventional assessments conducted in our clinic, it is almost impossible to identify patients with high polygenic risk, the prevalence of which is as 10 times frequent as that of FH [
      • Khera A.V.
      • Chaffin M.
      • Zekavat S.M.
      • Collins R.L.
      • Roselli C.
      • Natarajan P.
      • et al.
      Whole-genome sequencing to characterize monogenic and polygenic contributions in patients hospitalized with early-onset myocardial infarction.
      ].

      Keywords

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