학술논문
Fibromuscular Dysplasia and Abdominal Aortic Aneurysms Are Dimorphic Sex-Specific Diseases With Shared Complex Genetic Architecture.
Document Type
Academic Journal
Author
Katz AE; Department of Internal Medicine, Division of Cardiovascular Medicine (A.E.K., M.-L.Y., K.H., H.H., S.K.G.), University of Michigan, Ann Arbor.; Department of Human Genetics (A.E.K., M.-L.Y., K.H., H.H., J.A.D., J.Z.L., S.K.G.), University of Michigan, Ann Arbor.; Medical Genomics & Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD (A.E.K.).; Yang ML; Department of Internal Medicine, Division of Cardiovascular Medicine (A.E.K., M.-L.Y., K.H., H.H., S.K.G.), University of Michigan, Ann Arbor.; Department of Human Genetics (A.E.K., M.-L.Y., K.H., H.H., J.A.D., J.Z.L., S.K.G.), University of Michigan, Ann Arbor.; Department of Computational Medicine and Bioinformatics (M.-L.Y.), University of Michigan, Ann Arbor.; Levin MG; Corporal Michael J. Crescenz Philadelphia VA Medical Center (M.G.L., S.M.D.).; Division of Cardiovascular Medicine, Department of Medicine (M.G.L.).; Tcheandjieu C; Gladstone Institute of data science and Biotechnology, Gladstone Institutes; and Department of epidemiology and biostatistics, University of California at San Francisco, CA. (C.T.).; Mathis M; Department of Anesthesiology, Michigan Medicine (M.M., C.M.B.), University of Michigan, Ann Arbor.; Hunker K; Department of Internal Medicine, Division of Cardiovascular Medicine (A.E.K., M.-L.Y., K.H., H.H., S.K.G.), University of Michigan, Ann Arbor.; Department of Human Genetics (A.E.K., M.-L.Y., K.H., H.H., J.A.D., J.Z.L., S.K.G.), University of Michigan, Ann Arbor.; Blackburn S; Department of Surgery, Section of Vascular Surgery (S.B., J.L.E., D.M.C., M.K., J.C.S.), University of Michigan, Ann Arbor.; Eliason JL; Department of Surgery, Section of Vascular Surgery (S.B., J.L.E., D.M.C., M.K., J.C.S.), University of Michigan, Ann Arbor.; Coleman DM; Department of Surgery, Section of Vascular Surgery (S.B., J.L.E., D.M.C., M.K., J.C.S.), University of Michigan, Ann Arbor.; Fendrikova-Mahlay N; Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH (N.F.-M.).; Gornik HL; Harrington Heart and Vascular Institute, University Hospitals, Cleveland, OH (H.L.G.).; Karmakar M; Department of Surgery, Section of Vascular Surgery (S.B., J.L.E., D.M.C., M.K., J.C.S.), University of Michigan, Ann Arbor.; Hill H; Department of Internal Medicine, Division of Cardiovascular Medicine (A.E.K., M.-L.Y., K.H., H.H., S.K.G.), University of Michigan, Ann Arbor.; Department of Human Genetics (A.E.K., M.-L.Y., K.H., H.H., J.A.D., J.Z.L., S.K.G.), University of Michigan, Ann Arbor.; Xu C; Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor (C.X., M.Z., S.Z., X.Z.).; Zawistowski M; Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor (C.X., M.Z., S.Z., X.Z.).; Brummett CM; Department of Anesthesiology, Michigan Medicine (M.M., C.M.B.), University of Michigan, Ann Arbor.; Zoellner S; Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor (C.X., M.Z., S.Z., X.Z.).; Zhou X; Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor (C.X., M.Z., S.Z., X.Z.).; O'Donnell CJ; VA Boston Healthcare System (C.O.).; Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (C.O.).; Douglas JA; Department of Human Genetics (A.E.K., M.-L.Y., K.H., H.H., J.A.D., J.Z.L., S.K.G.), University of Michigan, Ann Arbor.; Assimes TL; VA Palo Alto Health Care System (T.L.A., P.S.T.).; Division of Cardiovascular Medicine, Department of Medicine (T.L.A.), Stanford University School of Medicine, CA.; Tsao PS; VA Palo Alto Health Care System (T.L.A., P.S.T.).; Li JZ; Department of Human Genetics (A.E.K., M.-L.Y., K.H., H.H., J.A.D., J.Z.L., S.K.G.), University of Michigan, Ann Arbor.; Damrauer SM; Corporal Michael J. Crescenz Philadelphia VA Medical Center (M.G.L., S.M.D.).; Department of Surgery and Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia (S.M.D.).; Stanley JC; Department of Surgery, Section of Vascular Surgery (S.B., J.L.E., D.M.C., M.K., J.C.S.), University of Michigan, Ann Arbor.; Ganesh SK; Department of Internal Medicine, Division of Cardiovascular Medicine (A.E.K., M.-L.Y., K.H., H.H., S.K.G.), University of Michigan, Ann Arbor.; Department of Human Genetics (A.E.K., M.-L.Y., K.H., H.H., J.A.D., J.Z.L., S.K.G.), University of Michigan, Ann Arbor.
Source
Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 101714113 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2574-8300 (Electronic) Linking ISSN: 25748300 NLM ISO Abbreviation: Circ Genom Precis Med Subsets: MEDLINE
Subject
Language
English
Abstract
Background: The risk of arterial diseases may be elevated among family members of individuals having multifocal fibromuscular dysplasia (FMD). We sought to investigate the risk of arterial diseases in families of individuals with FMD.
Methods: Family histories for 73 probands with FMD were obtained, which included an analysis of 463 total first-degree relatives focusing on FMD and related arterial disorders. A polygenic risk score for FMD (PRSFMD ) was constructed from prior genome-wide association findings of 584 FMD cases and 7139 controls and evaluated for association with an abdominal aortic aneurysm (AAA) in a cohort of 9693 AAA cases and 294 049 controls. A previously published PRS AAA was also assessed among the FMD cases and controls.
Results: Of all first degree relatives of probands, 9.3% were diagnosed with FMD, aneurysms, and dissections. Aneurysmal disease occurred in 60.5% of affected relatives and 5.6% of all relatives. Among 227 female first-degree relatives of probands, 4.8% (11) had FMD, representing a relative risk (RR)FMD of 1.5 ([95% CI, 0.75-2.8]; P =0.19) compared with the estimated population prevalence of 3.3%, though not of statistical significance. Of all fathers of FMD probands, 11% had AAAs resulting in a RR AAA of 2.3 ([95% CI, 1.12-4.6]; P =0.014) compared with population estimates. The PRS FMD was found to be associated with an AAA (odds ratio, 1.03 [95% CI, 1.01-1.05]; P =2.6×10 -3 ), and the PRS AAA was found to be associated with FMD (odds ratio, 1.53 [95% CI, 1.2-1.9]; P =9.0×10 -5 ) as well.
Conclusions: FMD and AAAs seem to be sex-dimorphic manifestations of a heritable arterial disease with a partially shared complex genetic architecture. Excess risk of having an AAA according to a family history of FMD may justify screening in family members of individuals having FMD.
Methods: Family histories for 73 probands with FMD were obtained, which included an analysis of 463 total first-degree relatives focusing on FMD and related arterial disorders. A polygenic risk score for FMD (PRS
Results: Of all first degree relatives of probands, 9.3% were diagnosed with FMD, aneurysms, and dissections. Aneurysmal disease occurred in 60.5% of affected relatives and 5.6% of all relatives. Among 227 female first-degree relatives of probands, 4.8% (11) had FMD, representing a relative risk (RR)
Conclusions: FMD and AAAs seem to be sex-dimorphic manifestations of a heritable arterial disease with a partially shared complex genetic architecture. Excess risk of having an AAA according to a family history of FMD may justify screening in family members of individuals having FMD.