Shared genetic architecture of hernias: A genome-wide association study with multivariable meta-analysis of multiple hernia phenotypes.
Abdominal hernias are common and characterised by the abnormal protrusion of a viscus through the wall of the abdominal cavity. The global incidence is 18.5 million annually and there are limited non-surgical treatments. To improve understanding of common hernia aetiopathology, we performed a six-st...
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0272261&type=printable |
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| author | Waheed Ul-Rahman Ahmed Manal I A Patel Michael Ng James McVeigh Krina Zondervan Akira Wiberg Dominic Furniss |
| author_facet | Waheed Ul-Rahman Ahmed Manal I A Patel Michael Ng James McVeigh Krina Zondervan Akira Wiberg Dominic Furniss |
| author_sort | Waheed Ul-Rahman Ahmed |
| collection | DOAJ |
| description | Abdominal hernias are common and characterised by the abnormal protrusion of a viscus through the wall of the abdominal cavity. The global incidence is 18.5 million annually and there are limited non-surgical treatments. To improve understanding of common hernia aetiopathology, we performed a six-stage genome-wide association study (GWAS) of 62,637 UK Biobank participants with either single or multiple hernia phenotypes including inguinal, femoral, umbilical and hiatus hernia. Additionally, we performed multivariable meta-analysis with metaUSAT, to allow integration of summary data across traits to generate combined effect estimates. On individual hernia analysis, we identified 3404 variants across 38 genome-wide significant (p < 5×10-8) loci of which 11 are previously unreported. Robust evidence for five shared susceptibility loci was discovered: ZC3H11B, EFEMP1, MHC region, WT1 and CALD1. Combined hernia phenotype analyses with additional multivariable meta-analysis of summary statistics in metaUSAT revealed 28 independent (seven previously unreported) shared susceptibility loci. These clustered in functional categories related to connective tissue and elastic fibre homeostasis. Weighted genetic risk scores also correlated with disease severity suggesting a phenotypic-genotypic severity correlation, an important finding to inform future personalised therapeutic approaches to hernia. |
| format | Article |
| id | doaj-art-14b6e6d77a3f4a50b1b9519048ccc7b9 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-14b6e6d77a3f4a50b1b9519048ccc7b92025-08-20T02:33:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-011712e027226110.1371/journal.pone.0272261Shared genetic architecture of hernias: A genome-wide association study with multivariable meta-analysis of multiple hernia phenotypes.Waheed Ul-Rahman AhmedManal I A PatelMichael NgJames McVeighKrina ZondervanAkira WibergDominic FurnissAbdominal hernias are common and characterised by the abnormal protrusion of a viscus through the wall of the abdominal cavity. The global incidence is 18.5 million annually and there are limited non-surgical treatments. To improve understanding of common hernia aetiopathology, we performed a six-stage genome-wide association study (GWAS) of 62,637 UK Biobank participants with either single or multiple hernia phenotypes including inguinal, femoral, umbilical and hiatus hernia. Additionally, we performed multivariable meta-analysis with metaUSAT, to allow integration of summary data across traits to generate combined effect estimates. On individual hernia analysis, we identified 3404 variants across 38 genome-wide significant (p < 5×10-8) loci of which 11 are previously unreported. Robust evidence for five shared susceptibility loci was discovered: ZC3H11B, EFEMP1, MHC region, WT1 and CALD1. Combined hernia phenotype analyses with additional multivariable meta-analysis of summary statistics in metaUSAT revealed 28 independent (seven previously unreported) shared susceptibility loci. These clustered in functional categories related to connective tissue and elastic fibre homeostasis. Weighted genetic risk scores also correlated with disease severity suggesting a phenotypic-genotypic severity correlation, an important finding to inform future personalised therapeutic approaches to hernia.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0272261&type=printable |
| spellingShingle | Waheed Ul-Rahman Ahmed Manal I A Patel Michael Ng James McVeigh Krina Zondervan Akira Wiberg Dominic Furniss Shared genetic architecture of hernias: A genome-wide association study with multivariable meta-analysis of multiple hernia phenotypes. PLoS ONE |
| title | Shared genetic architecture of hernias: A genome-wide association study with multivariable meta-analysis of multiple hernia phenotypes. |
| title_full | Shared genetic architecture of hernias: A genome-wide association study with multivariable meta-analysis of multiple hernia phenotypes. |
| title_fullStr | Shared genetic architecture of hernias: A genome-wide association study with multivariable meta-analysis of multiple hernia phenotypes. |
| title_full_unstemmed | Shared genetic architecture of hernias: A genome-wide association study with multivariable meta-analysis of multiple hernia phenotypes. |
| title_short | Shared genetic architecture of hernias: A genome-wide association study with multivariable meta-analysis of multiple hernia phenotypes. |
| title_sort | shared genetic architecture of hernias a genome wide association study with multivariable meta analysis of multiple hernia phenotypes |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0272261&type=printable |
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