No clear evidence for relationships of Apolipoprotein E genotype with measures of common infections in three UK cohorts DOI Creative Commons

Rebecca Green,

Alba Fernández‐Sanlés, Caterina Felici

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 18, 2024

Abstract APOE genotype is the strongest genetic risk factor for late onset Alzheimer’s disease, with ε2 and ε4 alleles decreasing increasing relative to ε3 allele, respectively. Although evidence has been conflicting, several common infections have associated disease risk, interactions by carriage also reported. Nevertheless, date, no study examined relationships between measures of multiple among large population-based studies. We investigated associations (i.e. non-carrier vs carrier) serostatus antibody titers 14 pathogens – encompassing herpesviruses, human polyomaviruses, C.trachomatis, H.pylori , T.gondii in three cohorts (UK Biobank, National Survey Health Development, Southall Brent Revisited). Pathogen was derived using validated cut-offs relevant antigens included as an outcome assessing previous infection. Antibody were dichotomised seropositive subset each antigen binary outcomes recent immunological responses. conducted analyses cohort mixed-models, including age, sex principal components fixed-effects, relatedness a random-effect. In secondary analyses, we additionally assessed i) dosage number copies allele interest), ii) continuous (rank-based inverse normal transformed). Findings meta-analysed across (n=10,059) random-effects models corrected tests false discovery rate. found clear or any pathogen, strong observed our following testing correction. Investigations genotypes clinical manifestations these pathogens, well expanding include other viruses such SARS-CoV-2, would be warranted.

Язык: Английский

Common infections and neuroimaging markers of dementia in three UK cohort studies DOI Creative Commons

Rebecca Green,

Carole H. Sudre, Charlotte Warren‐Gash

и другие.

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(3), С. 2128 - 2142

Опубликована: Янв. 22, 2024

Abstract INTRODUCTION We aimed to investigate associations between common infections and neuroimaging markers of dementia risk (brain volume, hippocampal white matter lesions) across three population‐based studies. METHODS tested serology measures (pathogen serostatus, cumulative burden, continuous antibody responses) outcomes using linear regression, including adjustments for total intracranial volume scanner/clinic information (basic model), age, sex, ethnicity, education, socioeconomic position, alcohol, body mass index, smoking (fully adjusted model). Interactions apolipoprotein E ( APOE ) genotype were tested. Findings meta‐analyzed cohorts N main = 2632; APOE‐interaction 1810). RESULTS Seropositivity John Cunningham virus associated with smaller brain volumes in basic models (β −3.89 mL [−5.81, −1.97], P < 0.05); these largely attenuated fully −1.59 [−3.55, 0.36], 0.11). No other relationships robust multiple testing corrections sensitivity analyses, but several suggestive observed. DISCUSSION did not find clear evidence risk. Some findings warrant replication.

Язык: Английский

Процитировано

2
No clear evidence for relationships of Apolipoprotein E genotype with measures of common infections in three UK cohorts DOI Creative Commons

Rebecca Green,

Alba Fernández‐Sanlés, Caterina Felici

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 18, 2024

Abstract APOE genotype is the strongest genetic risk factor for late onset Alzheimer’s disease, with ε2 and ε4 alleles decreasing increasing relative to ε3 allele, respectively. Although evidence has been conflicting, several common infections have associated disease risk, interactions by carriage also reported. Nevertheless, date, no study examined relationships between measures of multiple among large population-based studies. We investigated associations (i.e. non-carrier vs carrier) serostatus antibody titers 14 pathogens – encompassing herpesviruses, human polyomaviruses, C.trachomatis, H.pylori , T.gondii in three cohorts (UK Biobank, National Survey Health Development, Southall Brent Revisited). Pathogen was derived using validated cut-offs relevant antigens included as an outcome assessing previous infection. Antibody were dichotomised seropositive subset each antigen binary outcomes recent immunological responses. conducted analyses cohort mixed-models, including age, sex principal components fixed-effects, relatedness a random-effect. In secondary analyses, we additionally assessed i) dosage number copies allele interest), ii) continuous (rank-based inverse normal transformed). Findings meta-analysed across (n=10,059) random-effects models corrected tests false discovery rate. found clear or any pathogen, strong observed our following testing correction. Investigations genotypes clinical manifestations these pathogens, well expanding include other viruses such SARS-CoV-2, would be warranted.

Язык: Английский

Процитировано

0