Phenotypic findings associated with variation in elastin
Summary: Variation in the elastin gene (ELN) may contribute to connective tissue disease beyond the known disease associations of supravalvar aortic stenosis and cutis laxa. Exome data from MyCode Community Health Initiative participants were analyzed for ELN rare variants (mean allele frequency <...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | HGG Advances |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666247724001283 |
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| _version_ | 1846113086227873792 |
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| author | Anne Justice Melissa A. Kelly Gary Bellus Joshua D. Green Raza Zaidi Taylor Kerrins Navya Josyula Teresa R. Luperchio Beth A. Kozel Marc S. Williams |
| author_facet | Anne Justice Melissa A. Kelly Gary Bellus Joshua D. Green Raza Zaidi Taylor Kerrins Navya Josyula Teresa R. Luperchio Beth A. Kozel Marc S. Williams |
| author_sort | Anne Justice |
| collection | DOAJ |
| description | Summary: Variation in the elastin gene (ELN) may contribute to connective tissue disease beyond the known disease associations of supravalvar aortic stenosis and cutis laxa. Exome data from MyCode Community Health Initiative participants were analyzed for ELN rare variants (mean allele frequency <1%, not currently annotated as benign). Participants with variants of interest underwent phenotyping by dual chart review using a standardized abstraction tool. Additionally, all rare variants that met inclusion criteria were collapsed into an ELN gene burden score to perform a phenome-wide association study (PheWAS). Two hundred and ninety-six eligible participants with relevant ELN variants were identified from 184,293 MyCode participants. One hundred and three of 254 living participants (41%) met phenotypic criteria, most commonly aortic hypoplasia, arterial dilation, aneurysm, and dissection, and connective tissue abnormalities. ELN variation was significantly (p < 2.8 × 10−5) associated with “arterial dissection” in the PheWAS and two connective tissue Phecodes approached significance. Variation in ELN is associated with connective tissue pathology beyond classic phenotypes. |
| format | Article |
| id | doaj-art-9d2beb91907545de8bc98c1b4f54265e |
| institution | Kabale University |
| issn | 2666-2477 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | HGG Advances |
| spelling | doaj-art-9d2beb91907545de8bc98c1b4f54265e2024-12-22T05:29:50ZengElsevierHGG Advances2666-24772025-01-0161100388Phenotypic findings associated with variation in elastinAnne Justice0Melissa A. Kelly1Gary Bellus2Joshua D. Green3Raza Zaidi4Taylor Kerrins5Navya Josyula6Teresa R. Luperchio7Beth A. Kozel8Marc S. Williams9Department of Population Health, Geisinger, Danville, PA, USADepartment of Genomic Health, Geisinger, Danville, PA, USADepartment of Pediatrics, Geisinger, Danville, PA, USADepartment of Genomic Health, Geisinger, Rockville, MD, USADepartment of Internal Medicine, Geisinger, Danville, PA, USADepartment of Pediatrics, Geisinger, Danville, PA, USADepartment of Population Health, Geisinger, Danville, PA, USANational Heart, Lung, and Blood Institute, Bethesda, MD, USANational Heart, Lung, and Blood Institute, Bethesda, MD, USADepartment of Genomic Health, Geisinger, Danville, PA, USA; Corresponding authorSummary: Variation in the elastin gene (ELN) may contribute to connective tissue disease beyond the known disease associations of supravalvar aortic stenosis and cutis laxa. Exome data from MyCode Community Health Initiative participants were analyzed for ELN rare variants (mean allele frequency <1%, not currently annotated as benign). Participants with variants of interest underwent phenotyping by dual chart review using a standardized abstraction tool. Additionally, all rare variants that met inclusion criteria were collapsed into an ELN gene burden score to perform a phenome-wide association study (PheWAS). Two hundred and ninety-six eligible participants with relevant ELN variants were identified from 184,293 MyCode participants. One hundred and three of 254 living participants (41%) met phenotypic criteria, most commonly aortic hypoplasia, arterial dilation, aneurysm, and dissection, and connective tissue abnormalities. ELN variation was significantly (p < 2.8 × 10−5) associated with “arterial dissection” in the PheWAS and two connective tissue Phecodes approached significance. Variation in ELN is associated with connective tissue pathology beyond classic phenotypes.http://www.sciencedirect.com/science/article/pii/S2666247724001283elastinconnective tissuesupravalvar aortic stenosisaortic hypoplasiaarterial dissectionarterial dilation and aneurysm |
| spellingShingle | Anne Justice Melissa A. Kelly Gary Bellus Joshua D. Green Raza Zaidi Taylor Kerrins Navya Josyula Teresa R. Luperchio Beth A. Kozel Marc S. Williams Phenotypic findings associated with variation in elastin HGG Advances elastin connective tissue supravalvar aortic stenosis aortic hypoplasia arterial dissection arterial dilation and aneurysm |
| title | Phenotypic findings associated with variation in elastin |
| title_full | Phenotypic findings associated with variation in elastin |
| title_fullStr | Phenotypic findings associated with variation in elastin |
| title_full_unstemmed | Phenotypic findings associated with variation in elastin |
| title_short | Phenotypic findings associated with variation in elastin |
| title_sort | phenotypic findings associated with variation in elastin |
| topic | elastin connective tissue supravalvar aortic stenosis aortic hypoplasia arterial dissection arterial dilation and aneurysm |
| url | http://www.sciencedirect.com/science/article/pii/S2666247724001283 |
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