Fibromuscular Dysplasia and Abdominal Aortic Aneurysms Are Dimorphic Sex-Specific Diseases With Shared Complex Genetic Architecture

Alexander E Katz; Min-Lee Yang; Michael G Levin; Catherine Tcheandjieu; Michael Mathis; Kristina Hunker; Susan Blackburn; Jonathan L Eliason; Dawn M Coleman; Natalia Fendrikova-Mahlay; Heather L Gornik; Monita Karmakar; Hannah Hill; Chang Xu; Matthew Zawistowski; Chad M Brummett; Sebastian Zoellner; Xiang Zhou; Christopher J O'Donnell; Julie A Douglas; Themistocles L Assimes; Phillip S Tsao; Jun Z Li; Scott M Damrauer; James C Stanley; Santhi K Ganesh; VA Million Veteran Program

doi:10.1161/CIRCGEN.121.003496

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Fibromuscular Dysplasia and Abdominal Aortic Aneurysms Are Dimorphic Sex-Specific Diseases With Shared Complex Genetic Architecture

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Fibromuscular Dysplasia and Abdominal Aortic Aneurysms Are Dimorphic Sex-Specific Diseases With Shared Complex Genetic Architecture

Alexander E Katz, Min-Lee Yang, Michael G Levin, Catherine Tcheandjieu, Michael Mathis, Kristina Hunker, Susan Blackburn, Jonathan L Eliason, Dawn M Coleman, Natalia Fendrikova-Mahlay, …

Circulation. Genomic and precision medicine, Vol.15(6), pp.e003496-e003496

12/2022

DOI: 10.1161/CIRCGEN.121.003496

PMCID: PMC9772208

PMID: 36374587

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Abstract

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. 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 ) 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 was also assessed among the FMD cases and controls. 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) of 1.5 ([95% CI, 0.75-2.8]; =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 of 2.3 ([95% CI, 1.12-4.6]; =0.014) compared with population estimates. The PRS was found to be associated with an AAA (odds ratio, 1.03 [95% CI, 1.01-1.05]; =2.6×10 ), and the PRS was found to be associated with FMD (odds ratio, 1.53 [95% CI, 1.2-1.9]; =9.0×10 ) as well. 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.

Aortic Aneurysm, Abdominal - epidemiology

Aortic Aneurysm, Abdominal - genetics

Arteries

Female

Fibromuscular Dysplasia - complications

Fibromuscular Dysplasia - epidemiology

Fibromuscular Dysplasia - genetics

Genome-Wide Association Study

Humans

Male

Risk Factors

Details

Title: Subtitle: Fibromuscular Dysplasia and Abdominal Aortic Aneurysms Are Dimorphic Sex-Specific Diseases With Shared Complex Genetic Architecture
Creators: Alexander E Katz - University of Michigan
Min-Lee Yang - University of Michigan
Michael G Levin - Philadelphia VA Medical Center
Catherine Tcheandjieu - VA Palo Alto Health Care System
Michael Mathis - University of Michigan
Kristina Hunker - University of Michigan
Susan Blackburn - University of Michigan
Jonathan L Eliason - University of Michigan
Dawn M Coleman - University of Michigan
Natalia Fendrikova-Mahlay - University Hospitals of Cleveland
Heather L Gornik - University Hospitals of Cleveland
Monita Karmakar - University of Michigan
Hannah Hill - University of Michigan
Chang Xu - University of Michigan
Matthew Zawistowski - University of Michigan
Chad M Brummett - University of Michigan
Sebastian Zoellner - 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.)
Xiang Zhou - University of Michigan
Christopher J O'Donnell - VA Boston Healthcare System
Julie A Douglas - University of Michigan
Themistocles L Assimes - VA Palo Alto Health Care System
Phillip S Tsao - VA Palo Alto Health Care System
Jun Z Li - University of Michigan
Scott M Damrauer - Philadelphia VA Medical Center
James C Stanley - University of Michigan
Santhi K Ganesh - University of Michigan
VA Million Veteran Program
Contributors: Zuhair Ballas (Contributor) - University of Iowa, Immunology
Resource Type: Journal article
Publication Details: Circulation. Genomic and precision medicine, Vol.15(6), pp.e003496-e003496
DOI: 10.1161/CIRCGEN.121.003496
PMID: 36374587
PMCID: PMC9772208
NLM abbreviation: Circ Genom Precis Med
ISSN: 2574-8300
eISSN: 2574-8300
Grant note: R01 HL139672 / NHLBI NIH HHS 2013104 / Doris Duke Charitable Foundation R35 HL161016 / NHLBI NIH HHS
Language: English
Date published: 12/2022
Academic Unit: Immunology; Internal Medicine
Record Identifier: 9984359859302771

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