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Replication of an association of variation in the FOXO3A gene with human longevity using both case-control and longitudinal data.

ABSTRACT: Genetic variation in FOXO3A has previously been associated with human longevity. Studies published so far have been case-control studies and hence vulnerable to bias introduced by cohort effects. In this study we extended the previous findings in the cohorts of oldest old Danes (the Danish 1905 cohort, N=1089) and middle-aged Danes (N=736), applying a longitudinal study design as well as the case-control study design. Fifteen SNPs were chosen in order to cover the known common variation in FOXO3A. Comparing SNP frequencies in the oldest old with middle-aged individuals, we found association (after correction for multiple testing) of eight SNPs; 4 (rs13217795, rs2764264, rs479744, and rs9400239) previously reported to be associated with longevity and four novel SNPs (rs12206094, rs13220810, rs7762395, and rs9486902 (corrected P-values 0.001-0.044). Moreover, we found association of the haplotypes TAC and CAC of rs9486902, rs10499051, and rs12206094 (corrected P-values: 0.01-0.03) with longevity. Finally, we here present data applying a longitudinal study design; when using follow-up survival data on the oldest old in a longitudinal analysis, we found no SNPs to remain significant after the correction for multiple testing (Bonferroni correction). Hence, our results support and extent the proposed role of FOXO3A as a candidate longevity gene for survival from younger ages to old age, yet not during old age.

SUBMITTER: Soerensen M

PROVIDER: S-EPMC2992870 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Replication of an association of variation in the FOXO3A gene with human longevity using both case-control and longitudinal data.

Soerensen Mette M Dato Serena S Christensen Kaare K McGue Matt M Stevnsner Tinna T Bohr Vilhelm A VA Christiansen Lene L

Aging cell 20101021 6

Genetic variation in FOXO3A has previously been associated with human longevity. Studies published so far have been case-control studies and hence vulnerable to bias introduced by cohort effects. In this study we extended the previous findings in the cohorts of oldest old Danes (the Danish 1905 cohort, N=1089) and middle-aged Danes (N=736), applying a longitudinal study design as well as the case-control study design. Fifteen SNPs were chosen in order to cover the known common variation in FOXO3 ...[more]

PMID: 20849522

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Project description:BackgroundCOVID-19 epidemic has paralleled with the so called infodemic, where countless pieces of information have been disseminated on putative risk factors for COVID-19. Among those, emerged the notion that people suffering from autoimmune diseases (AIDs) have a higher risk of SARS-CoV-2 infection.MethodsThe cohort included all COVID-19 cases residents in the Agency for Health Protection (AHP) of Milan that, from the beginning of the outbreak, developed a web-based platform that traced positive and negative cases as well as related contacts. AIDs subjects were defined ad having one the following autoimmune disease: rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren disease, ankylosing spondylitis, myasthenia gravis, Hashimoto's disease, acquired autoimmune hemolytic anemia, and psoriatic arthritis. To investigate whether AID subjects are at increased risk of SARS-CoV-2 infection, and whether they have worse prognosis than AIDs-free subjects once infected, we performed a combined analysis of a test-negative design case-control study, a case-control with test-positive as cases, and one with test-negative as cases (CC-NEG).ResultsDuring the outbreak, the Milan AHP endured, up to April 27th 2020, 20,364 test-positive and 34,697 test-negative subjects. We found no association between AIDs and being positive to COVID-19, but a statistically significant association between AIDs and being negative to COVID-19 in the CC-NEG. If, as likely, test-negative subjects underwent testing because of respiratory infection symptoms, these results imply that autoimmune diseases may be a risk factor for respiratory infections in general (including COVID-19), but they are not a specific risk factor for COVID-19. Furthermore, when infected by SARS-CoV-2, AIDs subjects did not have a worse prognosis compared to non-AIDs subjects. Results highlighted a potential unbalance in the testing campaign, which may be correlated to the characteristics of the tested person, leading specific frail population to be particularly tested.ConclusionsLack of availability of sound scientific knowledge inevitably lead unreliable news to spread over the population, preventing people to disentangle them form reliable information. Even if additional studies are needed to replicate and strengthen our results, these findings represent initial evidence to derive recommendations based on actual data for subjects with autoimmune diseases.

Dataset Information

Replication of an association of variation in the FOXO3A gene with human longevity using both case-control and longitudinal data.

Publications

Replication of an association of variation in the FOXO3A gene with human longevity using both case-control and longitudinal data.

Similar Datasets

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