Genetic identification of familial hypercholesterolemia within a single US health care system

被引：308

作者：

Abul-Husn, Noura S. ^{[1
]}

Manickam, Kandamurugu ^{[2
]}

Jones, Laney K. ^{[2
]}

Wright, Eric A. ^{[2
]}

Hartzel, Dustin N. ^{[2
]}

Gonzaga-Jauregui, Claudia ^{[1
]}

O'Dushlaine, Colm ^{[1
]}

Leader, Joseph B. ^{[2
]}

Kirchner, H. Lester ^{[2
]}

Lindbuchler, D'Andra M. ^{[2
]}

Barr, Marci L. ^{[2
]}

Giovanni, Monica A. ^{[2
]}

Ritchie, Marylyn D. ^{[2
]}

Overton, John D. ^{[1
]}

Reid, Jeffrey G. ^{[1
]}

Metpally, Raghu P. R. ^{[2
]}

Wardeh, Amr H. ^{[2
]}

Borecki, Ingrid B. ^{[1
]}

Yancopoulos, George D. ^{[1
]}

Baras, Aris ^{[1
]}

Shuldiner, Alan R. ^{[1
]}

Gottesman, Omri ^{[1
]}

Ledbetter, David H. ^{[2
]}

Carey, David J. ^{[2
]}

Dewey, Frederick E. ^{[1
]}

Murray, Michael F. ^{[2
]}

机构：

[1] Regeneron Genet Ctr, Tarrytown, NY 10591 USA

[2] Geisinger Hlth Syst, Danville, PA 17822 USA

来源：

SCIENCE | 2016年 / 354卷 / 6319期

关键词：

ASSOCIATION EXPERT PANEL; GENERAL-POPULATION; PREVALENCE; MANAGEMENT; DIAGNOSIS; RECOMMENDATIONS; CHOLESTEROL; VARIANTS; GENOME; GUIDELINES;

D O I：

10.1126/science.aaf7000

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Familial hypercholesterolemia (FH) remains underdiagnosed despite widespread cholesterol screening. Exome sequencing and electronic health record (EHR) data of 50,726 individuals were used to assess the prevalence and clinical impact of FH-associated genomic variants in the Geisinger Health System. The estimated FH prevalence was 1: 256 in unselected participants and 1: 118 in participants ascertained via the cardiac catheterization laboratory. FH variant carriers had significantly increased risk of coronary artery disease. Only 24% of carriers met EHR-based presequencing criteria for probable or definite FH diagnosis. Active statin use was identified in 58% of carriers; 46% of statin-treated carriers had a low-density lipoprotein cholesterol level below 100 mg/dl. Thus, we find that genomic screening can prompt the diagnosis of FH patients, most of whom are receiving inadequate lipid-lowering therapy.

引用

页数：7

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