tetano
Editor, Senior Moderator
EBioMedicine
. 2021 Jul 22;70:103485.
doi: 10.1016/j.ebiom.2021.103485. Online ahead of print.
Shorter leukocyte telomere length is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank
Qingning Wang[SUP] 1 [/SUP], Veryan Codd[SUP] 1 [/SUP], Zahra Raisi-Estabragh[SUP] 2 [/SUP], Crispin Musicha[SUP] 3 [/SUP], Vasiliki Bountziouka[SUP] 3 [/SUP], Stephen Kaptoge[SUP] 4 [/SUP], Elias Allara[SUP] 5 [/SUP], Emanuele Di Angelantonio[SUP] 6 [/SUP], Adam S Butterworth[SUP] 6 [/SUP], Angela M Wood[SUP] 7 [/SUP], John R Thompson[SUP] 8 [/SUP], Steffen E Petersen[SUP] 2 [/SUP], Nicholas C Harvey[SUP] 9 [/SUP], John N Danesh[SUP] 10 [/SUP], Nilesh J Samani[SUP] 1 [/SUP], Christopher P Nelson[SUP] 11 [/SUP]
Affiliations
Abstract
Background Older age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain whether leucocyte telomere length (LTL), previously proposed as a marker of biological age, is also associated with COVID-19 outcomes. Methods We associated LTL values obtained from participants recruited into UK Biobank (UKB) during 2006-2010 with adverse COVID-19 outcomes recorded by 30 November 2020, defined as a composite of any of the following: hospital admission, need for critical care, respiratory support, or mortality. Using information on 130 LTL-associated genetic variants, we conducted exploratory Mendelian randomisation (MR) analyses in UKB to evaluate whether observational associations might reflect cause-and-effect relationships. Findings Of 6775 participants in UKB who tested positive for infection with SARS-CoV-2 in the community, there were 914 (13.5%) with adverse COVID-19 outcomes. The odds ratio (OR) for adverse COVID-19 outcomes was 1·17 (95% CI 1·05-1·30; P = 0·004) per 1-SD shorter usual LTL, after adjustment for age, sex and ethnicity. Similar ORs were observed in analyses that: adjusted for additional risk factors; disaggregated the composite outcome and reduced the scope for selection or collider bias. In MR analyses, the OR for adverse COVID-19 outcomes was directionally concordant but non-significant. Interpretation Shorter LTL is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including age. Further data are needed to determine whether this association reflects causality. Funding UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation.
. 2021 Jul 22;70:103485.
doi: 10.1016/j.ebiom.2021.103485. Online ahead of print.
Shorter leukocyte telomere length is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank
Qingning Wang[SUP] 1 [/SUP], Veryan Codd[SUP] 1 [/SUP], Zahra Raisi-Estabragh[SUP] 2 [/SUP], Crispin Musicha[SUP] 3 [/SUP], Vasiliki Bountziouka[SUP] 3 [/SUP], Stephen Kaptoge[SUP] 4 [/SUP], Elias Allara[SUP] 5 [/SUP], Emanuele Di Angelantonio[SUP] 6 [/SUP], Adam S Butterworth[SUP] 6 [/SUP], Angela M Wood[SUP] 7 [/SUP], John R Thompson[SUP] 8 [/SUP], Steffen E Petersen[SUP] 2 [/SUP], Nicholas C Harvey[SUP] 9 [/SUP], John N Danesh[SUP] 10 [/SUP], Nilesh J Samani[SUP] 1 [/SUP], Christopher P Nelson[SUP] 11 [/SUP]
Affiliations
- PMID: 34304048
- DOI: 10.1016/j.ebiom.2021.103485
Abstract
Background Older age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain whether leucocyte telomere length (LTL), previously proposed as a marker of biological age, is also associated with COVID-19 outcomes. Methods We associated LTL values obtained from participants recruited into UK Biobank (UKB) during 2006-2010 with adverse COVID-19 outcomes recorded by 30 November 2020, defined as a composite of any of the following: hospital admission, need for critical care, respiratory support, or mortality. Using information on 130 LTL-associated genetic variants, we conducted exploratory Mendelian randomisation (MR) analyses in UKB to evaluate whether observational associations might reflect cause-and-effect relationships. Findings Of 6775 participants in UKB who tested positive for infection with SARS-CoV-2 in the community, there were 914 (13.5%) with adverse COVID-19 outcomes. The odds ratio (OR) for adverse COVID-19 outcomes was 1·17 (95% CI 1·05-1·30; P = 0·004) per 1-SD shorter usual LTL, after adjustment for age, sex and ethnicity. Similar ORs were observed in analyses that: adjusted for additional risk factors; disaggregated the composite outcome and reduced the scope for selection or collider bias. In MR analyses, the OR for adverse COVID-19 outcomes was directionally concordant but non-significant. Interpretation Shorter LTL is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including age. Further data are needed to determine whether this association reflects causality. Funding UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation.