Fibromuscular Dysplasia and Abdominal Aortic Aneurysms Are Dimorphic Sex-Specific Diseases With Shared Complex Genetic Architecture. (14th November 2022)

• Record Type: Journal Article
• Authors: Katz, Alexander E.; Yang, Min-Lee; Levin, Michael G.; Tcheandjieu, Catherine; Mathis, Michael; Hunker, Kristina; Blackburn, Susan; Eliason, Jonathan L.; Coleman, Dawn M.; Fendrikova-Mahlay, Natalia; Gornik, Heather L.; Karmakar, Monita; Hill, Hannah; Xu, Chang; Zawistowski, Matthew; Brummett, Chad M.; Zoellner, Sebastian; Zhou, Xiang; O'Donnell, Christopher J.; Douglas, Julie A.; Assimes, Themistocles L.; Tsao, Phillip S.; Li, Jun Z.; Damrauer, Scott M.; Stanley, James C.; Ganesh, Santhi K.
• Other Names: Gaziano J. Michael author non-byline.; Muralidhar Sumitra author non-byline.; Ramoni Rachel author non-byline.; Beckham Jean author non-byline.; Chang Kyong-Mi author non-byline.; O'Donnell Christopher J. author non-byline.; Tsao Philip S. author non-byline.; Breeling James author non-byline.; Huang Grant author non-byline.; Casas Juan P. author non-byline.; Muralidhar Sumitra author non-byline.; Moser Jennifer author non-byline.; Whitbourne Stacey B. author non-byline.; Brewer Jessica V. author non-byline.; Aslan Mihaela author non-byline.; Connor Todd author non-byline.; Argyres Dean P. author non-byline.; Tsao Philip S. author non-byline.; Gaziano J. Michael author non-byline.; Stephens Brady author non-byline.; Brophy Mary T. author non-byline.; Humphries Donald E. author non-byline.; Selva Luis E. author non-byline.; Do Nhan author non-byline.; Shayan Shahpoor (Alex) author non-byline.; Cho Kelly author non-byline.; Churby Lori author non-byline.; O'Donnell Christopher J. author non-byline.; O'Donnell Christopher J. author non-byline.; Pyarajan Saiju author non-byline.; Tsao Philip S. author non-byline.; Cho Kelly author non-byline.; DuVall Scott L. author non-byline.; Pyarajan Saiju author non-byline.; Hauser Elizabeth author non-byline.; Sun Yan author non-byline.; Zhao Hongyu author non-byline.; Wilson Peter author non-byline.; McArdle Rachel author non-byline.; Dellitalia Louis author non-byline.; Mattocks Kristin author non-byline.; Harley John author non-byline.; Whittle Jeffrey author non-byline.; Jacono Frank author non-byline.; Beckham Jean author non-byline.; Wells John author non-byline.; Gutierrez Salvador author non-byline.; Gibson Gretchen author non-byline.; Hammer Kimberly author non-byline.; Kaminsky Laurence author non-byline.; Villareal Gerardo author non-byline.; Kinlay Scott author non-byline.; Xu Junzhe author non-byline.; Hamner Mark author non-byline.; Mathew Roy author non-byline.; Bhushan Sujata author non-byline.; Iruvanti Pran author non-byline.; Godschalk Michael author non-byline.; Ballas Zuhair author non-byline.; Ivins Douglas author non-byline.; Mastorides Stephen author non-byline.; Moorman Jonathan author non-byline.; Gappy Saib author non-byline.; Klein Jon author non-byline.; Ratcliffe Nora author non-byline.; Florez Hermes author non-byline.; Okusaga Olaoluwa author non-byline.; Murdoch Maureen author non-byline.; Sriram Peruvemba author non-byline.; Yeh Shing Shing author non-byline.; Tandon Neeraj author non-byline.; Jhala Darshana author non-byline.; Aguayo Samuel author non-byline.; Cohen David author non-byline.; Sharma Satish author non-byline.; Liangpunsakul Suthat author non-byline.; Oursler Kris Ann author non-byline.; Whooley Mary author non-byline.; Ahuja Sunil author non-byline.; Constans Joseph author non-byline.; Meyer Paul author non-byline.; Greco Jennifer author non-byline.; Rauchman Michael author non-byline.; Servatius Richard author non-byline.; Gaddy Melinda author non-byline.; Wallbom Agnes author non-byline.; Morgan Timothy author non-byline.; Stapley Todd author non-byline.; Sherman Scott author non-byline.; Ross George author non-byline.; Tsao Philip author non-byline.; Strollo Patrick author non-byline.; Boyko Edward author non-byline.; Meyer Laurence author non-byline.; Gupta Samir author non-byline.; Huq Mostaqul author non-byline.; Fayad Joseph author non-byline.; Hung Adriana author non-byline.; Lichy Jack author non-byline.; Hurley Robin author non-byline.; Robey Brooks author non-byline.; Striker Robert author non-byline.;
• Is Part Of: Circulation. Volume 15:Number 6(2022)
• Page Start: e003496
• Publication Date: 2022-11-14
• Subjects: aneurysm -- aortic aneurysm, abdominal -- arteries -- dissection -- fibromuscular dysplasia -- genetics -- sex dimorphism; Cardiovascular system -- Diseases -- Periodicals; Cardiovascular system -- Genetics -- Periodicals; Cardiovascular Diseases -- genetics; Precision Medicine; Periodical; Fulltext; Internet Resources; Periodicals; Electronic journals; Periodicals; 616.1042
• DOI: 10.1161/CIRCGEN.121.003496
• Languages: English
• ISSNs: 2574-8300

Abstract

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 PRSAAA 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 RRAAA of 2.3 ([95% CI, 1.12–4.6]; P =0.014) compared with population estimates. The PRSFMD 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 PRSAAA 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.