title: Genetic identification of familial hypercholesterolemia within a single U.S. health care system.
abstract: 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.
authors.affiliation: Regeneron Genetics Center, Tarrytown, NY 10591, USA.
authors.forename: Noura S
authors.initials: NS
authors.lastname: Abul-Husn
authors.affiliation: Geisinger Health System, Danville, PA 17822, USA.
authors.forename: Kandamurugu
authors.initials: K
authors.lastname: Manickam
authors.affiliation: Geisinger Health System, Danville, PA 17822, USA.
authors.forename: Laney K
authors.initials: LK
authors.lastname: Jones
authors.affiliation: Geisinger Health System, Danville, PA 17822, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Wright
authors.affiliation: Geisinger Health System, Danville, PA 17822, USA.
authors.forename: Dustin N
authors.initials: DN
authors.lastname: Hartzel
authors.affiliation: Regeneron Genetics Center, Tarrytown, NY 10591, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gonzaga-Jauregui
authors.affiliation: Regeneron Genetics Center, Tarrytown, NY 10591, USA.
authors.forename: Colm
authors.initials: C
authors.lastname: O'Dushlaine
authors.affiliation: Geisinger Health System, Danville, PA 17822, USA.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Leader
authors.affiliation: Geisinger Health System, Danville, PA 17822, USA.
authors.forename: H
authors.initials: H
authors.lastname: Lester Kirchner
authors.affiliation: Geisinger Health System, Danville, PA 17822, USA.
authors.forename: D'Andra M
authors.initials: DM
authors.lastname: Lindbuchler
authors.affiliation: Geisinger Health System, Danville, PA 17822, USA.
authors.forename: Marci L
authors.initials: ML
authors.lastname: Barr
authors.affiliation: Geisinger Health System, Danville, PA 17822, USA.
authors.forename: Monica A
authors.initials: MA
authors.lastname: Giovanni
authors.affiliation: Geisinger Health System, Danville, PA 17822, USA.
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.affiliation: Regeneron Genetics Center, Tarrytown, NY 10591, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Overton
authors.affiliation: Regeneron Genetics Center, Tarrytown, NY 10591, USA.
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Reid
authors.affiliation: Geisinger Health System, Danville, PA 17822, USA.
authors.forename: Raghu P R
authors.initials: RP
authors.lastname: Metpally
authors.affiliation: Geisinger Health System, Danville, PA 17822, USA.
authors.forename: Amr H
authors.initials: AH
authors.lastname: Wardeh
authors.affiliation: Regeneron Genetics Center, Tarrytown, NY 10591, USA.
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.affiliation: Regeneron Genetics Center, Tarrytown, NY 10591, USA.
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.affiliation: Regeneron Genetics Center, Tarrytown, NY 10591, USA.
authors.forename: Aris
authors.initials: A
authors.lastname: Baras
authors.affiliation: Regeneron Genetics Center, Tarrytown, NY 10591, USA.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
authors.affiliation: Regeneron Genetics Center, Tarrytown, NY 10591, USA.
authors.forename: Omri
authors.initials: O
authors.lastname: Gottesman
authors.affiliation: Geisinger Health System, Danville, PA 17822, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Ledbetter
authors.affiliation: Geisinger Health System, Danville, PA 17822, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Carey
authors.affiliation: Regeneron Genetics Center, Tarrytown, NY 10591, USA.
authors.forename: Frederick E
authors.initials: FE
authors.lastname: Dewey
authors.affiliation: Geisinger Health System, Danville, PA 17822, USA. mfmurray1@geisinger.edu.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Murray
mesh_terms: D004396:Coloring Agents / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000453:epidemiology; D003695:Delivery of Health Care; D004363:Drug Utilization / Q000706:statistics & numerical data*; D057286:Electronic Health Records; D059472:Exome / Q000235:genetics; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000097:blood; D015995:Prevalence; D014481:United States / Q000453:epidemiology
chemical_list: D004396:Coloring Agents; D008077:Lipoproteins, LDL