Background Hospitalized COVID-19 patients tend to be older and frequently have hypertension, diabetes or coronary heart disease (CHD), but whether these co-morbidities are true risk factors (i.e. more common than in the general older population) is unclear. We estimated associations between pre-existing diagnoses and hospitalized COVID-19 alone or with mortality, in a large community cohort. Methods UK Biobank (England) participants with baseline assessment 2006 to 2010, followed in hospital discharge records to 2017 and death records to 2020. Demographic and pre-existing common diagnoses association tested with hospitalized laboratory confirmed COVID-19 (16th March to 26th April 2020), alone or with mortality, in logistic models. Results Of 269,070 participants aged 65+, 507 (0.2%) became COVID-19 hospital inpatients, of which 141 (27.8%) died. Common co-morbidities in hospitalized inpatients were hypertension (59.6%), history of fall or fragility fractures (29.4%), coronary heart disease (CHD, 21.5%), type 2 diabetes (type 2, 19. 9%) and asthma (17.6%). However, in models adjusted for comorbidities, age-group, sex, ethnicity and education, pre-existing diagnoses of dementia, type 2 diabetes, COPD, pneumonia, depression, atrial fibrillation and hypertension emerged as independent risk factors for COVID-19 hospitalization, the first five remaining statistically significant for related mortality. Chronic Kidney Disease and asthma were risk factors for COVID-19 hospitalization in women but not men. Conclusion There are specific high risk pre-existing co-morbidities for COVID-19 hospitalization and related deaths in community based older men and women. These results do not support simple age-based targeting of the older population to prevent severe COVID-19 infections.

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Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status, has been reported. We present a pooled analysis (n=21,160) demonstrating associations between late AMD and APOε4 (OR=0.72 per haplotype; CI: 0.65–0.74; P=4.41×10−11) and APOε2 (OR=1.83 for homozygote carriers; CI: 1.04–3.23; P=0.04), following adjustment for age-group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR=1.54; CI: 1.38–1.72; P=2.8×10−15) and atrophic (OR=1.38; CI: 1.18–1.61; P=3.37×10−5) AMD but not early AMD (OR=0.94; CI: 0.86–1.03; P=0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyondε2 and ε4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology.

Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1p = 4 × 10−17), arthritis (GDF5p = 4 × 10−13), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing.

Variation in the apolipoprotein E gene (APOE) has been reported to be associated with longevity in humans. The authors assessed the allelic distribution of APOE isoforms ε2, ε3, and ε4 among 10,623 participants from 15 case-control and cohort studies of age-related macular degeneration (AMD) in populations of European ancestry (study dates ranged from 1990 to 2009). The authors included only the 10,623 control subjects from these studies who were classified as having no evidence of AMD, since variation within the APOE gene has previously been associated with AMD. In an analysis stratified by study center, gender, and smoking status, there was a decreasing frequency of the APOE ε4 isoform with increasing age (χ(2) for trend = 14.9 (1 df); P = 0.0001), with a concomitant increase in the ε3 isoform (χ(2) for trend = 11.3 (1 df); P = 0.001). The association with age was strongest in ε4 homozygotes; the frequency of ε4 homozygosity decreased from 2.7% for participants aged 60 years or less to 0.8% for those over age 85 years, while the proportion of participants with the ε3/ε4 genotype decreased from 26.8% to 17.5% across the same age range. Gender had no significant effect on the isoform frequencies. This study provides strong support for an association of the APOE gene with human longevity.