Associations Between Mosaic Loss of Sex Chromosomes and Incident Hospitalization for Atrial Fibrillation in the United Kingdom
Background Mosaic loss of chromosome Y (mLOY) in leukocytes of men reflects genomic instability from aging, smoking, and environmental exposures. A similar mosaic loss of chromosome X (mLOX) occurs among women. However, the associations between mLOY, mLOX, and risk of incident heart diseases are unc...
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| Language: | English |
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Wiley
2024-11-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.124.036984 |
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| author | Jungeun Lim Aubrey K. Hubbard Batel Blechter Jianxin Shi Weiyin Zhou Erikka Loftfield Mitchell J. Machiela Jason Y.Y. Wong |
| author_facet | Jungeun Lim Aubrey K. Hubbard Batel Blechter Jianxin Shi Weiyin Zhou Erikka Loftfield Mitchell J. Machiela Jason Y.Y. Wong |
| author_sort | Jungeun Lim |
| collection | DOAJ |
| description | Background Mosaic loss of chromosome Y (mLOY) in leukocytes of men reflects genomic instability from aging, smoking, and environmental exposures. A similar mosaic loss of chromosome X (mLOX) occurs among women. However, the associations between mLOY, mLOX, and risk of incident heart diseases are unclear. Methods and Results We estimated associations between mLOY, mLOX, and risk of incident heart diseases requiring hospitalization, including atrial fibrillation, myocardial infarction, ischemic heart disease, cardiomyopathy, and heart failure. We analyzed 190 613 men and 224 853 women with genotyping data from the UK Biobank. Among these participants, there were 37 037 men with mLOY and 13 978 women with mLOX detected using the Mosaic Chromosomal Alterations caller. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs of each incident heart disease in relation to mLOY in men and mLOX in women. Additionally, Mendelian randomization was conducted to estimate causal associations. Among men, detectable mLOY was associated with elevated risk of atrial fibrillation (HR, 1.06 [95% CI, 1.03–1.11]). The associations were apparent in both never smokers (HR, 1.07 [95% CI, 1.01–1.14]) and ever smokers (HR, 1.05 [95% CI, 1.01–1.11]) as well as men aged >60 and ≤60 years. Mendelian randomization analyses supported causal associations between mLOY and atrial fibrillation (HRMR‐PRESSO, 1.15 [95% CI, 1.13–1.18]). Among postmenopausal women, we found a suggestive inverse association between detectable mLOX and atrial fibrillation risk (HR, 0.90 [95% CI, 0.83–0.98]). However, associations with mLOY and mLOX were not found for other heart diseases. Conclusions Our findings suggest that mLOY and mLOX reflect sex‐specific biological processes or exposure profiles related to incident atrial fibrillation requiring hospitalization. |
| format | Article |
| id | doaj-art-04b91a8677994c66a15328818f6e43f5 |
| institution | Kabale University |
| issn | 2047-9980 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-04b91a8677994c66a15328818f6e43f52024-11-19T12:31:39ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-11-01132210.1161/JAHA.124.036984Associations Between Mosaic Loss of Sex Chromosomes and Incident Hospitalization for Atrial Fibrillation in the United KingdomJungeun Lim0Aubrey K. Hubbard1Batel Blechter2Jianxin Shi3Weiyin Zhou4Erikka Loftfield5Mitchell J. Machiela6Jason Y.Y. Wong7Epidemiology and Community Health Branch, National Heart, Lung, and Blood Institute Bethesda MDDivision of Cancer Epidemiology and Genetics National Cancer Institute Rockville MDDivision of Cancer Epidemiology and Genetics National Cancer Institute Rockville MDDivision of Cancer Epidemiology and Genetics National Cancer Institute Rockville MDDivision of Cancer Epidemiology and Genetics National Cancer Institute Rockville MDDivision of Cancer Epidemiology and Genetics National Cancer Institute Rockville MDDivision of Cancer Epidemiology and Genetics National Cancer Institute Rockville MDEpidemiology and Community Health Branch, National Heart, Lung, and Blood Institute Bethesda MDBackground Mosaic loss of chromosome Y (mLOY) in leukocytes of men reflects genomic instability from aging, smoking, and environmental exposures. A similar mosaic loss of chromosome X (mLOX) occurs among women. However, the associations between mLOY, mLOX, and risk of incident heart diseases are unclear. Methods and Results We estimated associations between mLOY, mLOX, and risk of incident heart diseases requiring hospitalization, including atrial fibrillation, myocardial infarction, ischemic heart disease, cardiomyopathy, and heart failure. We analyzed 190 613 men and 224 853 women with genotyping data from the UK Biobank. Among these participants, there were 37 037 men with mLOY and 13 978 women with mLOX detected using the Mosaic Chromosomal Alterations caller. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs of each incident heart disease in relation to mLOY in men and mLOX in women. Additionally, Mendelian randomization was conducted to estimate causal associations. Among men, detectable mLOY was associated with elevated risk of atrial fibrillation (HR, 1.06 [95% CI, 1.03–1.11]). The associations were apparent in both never smokers (HR, 1.07 [95% CI, 1.01–1.14]) and ever smokers (HR, 1.05 [95% CI, 1.01–1.11]) as well as men aged >60 and ≤60 years. Mendelian randomization analyses supported causal associations between mLOY and atrial fibrillation (HRMR‐PRESSO, 1.15 [95% CI, 1.13–1.18]). Among postmenopausal women, we found a suggestive inverse association between detectable mLOX and atrial fibrillation risk (HR, 0.90 [95% CI, 0.83–0.98]). However, associations with mLOY and mLOX were not found for other heart diseases. Conclusions Our findings suggest that mLOY and mLOX reflect sex‐specific biological processes or exposure profiles related to incident atrial fibrillation requiring hospitalization.https://www.ahajournals.org/doi/10.1161/JAHA.124.036984atrial fibrillationheart diseaseincident relative riskmosaic loss of sex chromosomesprospective cohort study |
| spellingShingle | Jungeun Lim Aubrey K. Hubbard Batel Blechter Jianxin Shi Weiyin Zhou Erikka Loftfield Mitchell J. Machiela Jason Y.Y. Wong Associations Between Mosaic Loss of Sex Chromosomes and Incident Hospitalization for Atrial Fibrillation in the United Kingdom Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease atrial fibrillation heart disease incident relative risk mosaic loss of sex chromosomes prospective cohort study |
| title | Associations Between Mosaic Loss of Sex Chromosomes and Incident Hospitalization for Atrial Fibrillation in the United Kingdom |
| title_full | Associations Between Mosaic Loss of Sex Chromosomes and Incident Hospitalization for Atrial Fibrillation in the United Kingdom |
| title_fullStr | Associations Between Mosaic Loss of Sex Chromosomes and Incident Hospitalization for Atrial Fibrillation in the United Kingdom |
| title_full_unstemmed | Associations Between Mosaic Loss of Sex Chromosomes and Incident Hospitalization for Atrial Fibrillation in the United Kingdom |
| title_short | Associations Between Mosaic Loss of Sex Chromosomes and Incident Hospitalization for Atrial Fibrillation in the United Kingdom |
| title_sort | associations between mosaic loss of sex chromosomes and incident hospitalization for atrial fibrillation in the united kingdom |
| topic | atrial fibrillation heart disease incident relative risk mosaic loss of sex chromosomes prospective cohort study |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.124.036984 |
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