Polygenic Versus Monogenic Causes of Hypercholesterolemia Ascertained Clinically

• DOI: 10.1161/atvbaha.116.308027
• Publication Date: 2016-10-21T02:59:32Z
• Authors: Jian Wang; Jacqueline S. Dron; Matthew R. Ban; John F. Robinson; Adam D. McIntyre; Maher Alazzam; Pei Jun Zhao; Allison A. Dilliott; Henian Cao; Murray W. Huff; David Rhainds; Cécile Low-Kam; Marie-Pierre Dubé; Guillaume Lettre; Jean-Claude Tardif; Robert A. Hegele
• Keywords: Adult; Genetic Markers; Male; Heterozygote; Multifactorial Inheritance; Heredity; DNA Copy Number Variations; DNA Mutational Analysis; Gene Dosage; High-Throughput Nucleotide Sequencing; Cholesterol, LDL; Middle Aged; 3. Good health; Hyperlipoproteinemia Type II; 03 medical and health sciences; 0302 clinical medicine; Mutation; Humans; Female; Genetic Predisposition to Disease; Genetic Testing; Biomarkers; Aged

Objective— Next-generation sequencing technology is transforming our understanding of heterozygous familial hypercholesterolemia, including revision prevalence estimates and attribution polygenic effects. Here, we examined the contributions monogenic factors in patients with severe hypercholesterolemia referred to a specialty clinic. Approach Results— We applied targeted next-generation custom annotation, coupled evaluation large-scale copy number variation scores for raised low-density lipoprotein cholesterol cohort 313 individuals defined as >5.0 mmol/L (>194 mg/dL). found that (1) hypercholesterolemia–causing mutations detected by were present 47.3% individuals; (2) percentage increased 53.7% when variations included; (3) further 67.1% extreme (4) an identified genetic component from 57.0% 92.0% level 5.0 >8.0 (194 >310 Conclusions— In clinically ascertained sample most had discrete basis using comprehensive screening approach includes sequencing, assay variations, trait scores.