English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Forkhead box O3A ( FOXOA3)  and apolipoprotein E ( APOE ) are arguably the strongest gene candidates to influence human exceptional longevity (EL, i.e., being a centenarian), but inconsistency exists among cohorts. Epistasis, defined as the effect of one locus being dependent on the presence of ‘modifier genes’, may contribute to explain the missing heritability of complex phenotypes such as EL. We assessed the potential association of epistasis among candidate polymorphisms related to physical capacity, as well as antioxidant defense and cardiometabolic traits, and EL in the Japanese population. A total of 1565 individuals were studied, subdivided into 822 middle-aged controls and 743 centenarians.    Results  We found a  FOXOA3  rs2802292 T-allele-dependent association of fibronectin type III domain-containing 5 ( FDNC5 ) rs16835198 with EL: the frequency of carriers of the  FOXOA3  rs2802292 T-allele among individuals with the rs16835198 GG genotype was significantly higher in cases than in controls ( P  < 0.05). On the other hand, among non-carriers of the  APOE  ‘risk’ ε4-allele, the frequency of the  FDNC5  rs16835198 G-allele was higher in cases than in controls (48.4% vs. 43.6%,  P  < 0.05). Among carriers of the ‘non-risk’  APOE  ε2-allele, the frequency of the rs16835198 G-allele was higher in cases than in controls (49% vs. 37.3%,  P  < 0.05).    Conclusions  The association of  FDNC5  rs16835198 with EL seems to depend on the presence of the  FOXOA3  rs2802292 T-allele and we report a novel association between  FNDC5  rs16835198 stratified by the presence of the  APOE  ε2/ε4-allele and EL. More research on ‘gene*gene’ and ‘gene*environment’ effects is needed in the field of EL.

Epistasis, physical capacity-related genes and exceptional longevity: FNDC5 gene interactions with candidate genes FOXOA3 and APOE