Age and Sex Differences in the Genetics of Cardiomyopathy
Genomics England Research Consortium,
Posted 08 Apr 2021
medRxiv DOI: 10.1101/2021.04.06.21255002
Posted 08 Apr 2021
Aims: Cardiomyopathy is a clinically and genetically heterogeneous disorder with age and sex-related differences in severity and outcomes. The aim of our study was to identify age and sex-related differences in the genetic architecture of cardiomyopathy. Methods and Results: We analyzed whole genome sequence data from 471 pediatric and 926 adult cardiomyopathy patients from our Heart Centre Biobank and from the Genomics England cohort. Overall yield of rare deleterious coding variants was higher in pediatric compared to adult onset cardiomyopathy, but not different by sex. MYH7, TNNT2, MYL3, and VCL variants were more frequent in pediatric patients; TTN and OBSCN variants were more frequent in adult patients, with MYH7 (Odds ratio 3.6; CI 2.1-6.3) and OBSCN (Odds ratio 5.5, CI 2.0-21.4) remaining significant after adjusting for multiple testing. Variants in early-onset cardiomyopathy clustered in highly constrained coding regions compared to those in adult patients (p=3.9x10-3). There were also differences between pediatric and adult patients in variant location within MYH7 and TTN genes. When analyzed by sex, variants in female compared to male patients were in more highly constrained coding regions (p=0.002). Conclusion: Our findings highlight under-appreciated genetic differences in early versus late onset cardiomyopathy. Variants in childhood cardiomyopathy and in female patients were in highly constrained coding regions of the genome suggesting greater deleterious effects and strong purifying selection in the general population. Knowledge of the affected gene, variant location within the gene, and variant constraint scores may be useful in predicting early versus late onset cardiomyopathy.
- Downloaded 157 times
- Download rankings, all-time:
- Site-wide: 142,461
- In genetic and genomic medicine: 826
- Year to date:
- Site-wide: 57,113
- Since beginning of last month:
- Site-wide: 69,804
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!