CADM2

Cell adhesion molecule 2 precursor (Immunoglobulin superfamily member 4D) (IgSF4D) (Nectin-like protein 3) (NECL-3) (Synaptic cell adhesion molecule 2) (SynCAM 2) [IGSF4D] [NECL3]

Publications

GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy.

PubMed

Full text

The genetic contribution to longevity in humans has been estimated to range from 15% to 25%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies. We conducted a meta-analysis of genome-wide association studies including 6,036 longevity cases, age ≥90 years, and 3,757 controls that died between ages 55 and 80 years. We additionally attempted to replicate earlier identified single nucleotide polymorphism (SNP) associations with longevity. In our meta-analysis, we found suggestive evidence for the association of SNPs near CADM2 (odds ratio [OR] = 0.81; p value = 9.66 × 10(-7)) and GRIK2 (odds ratio = 1.24; p value = 5.09 × 10(-8)) with longevity. When attempting to replicate findings earlier identified in genome-wide association studies, only the APOE locus consistently replicated. In an additional look-up of the candidate gene FOXO3, we found that an earlier identified variant shows a highly significant association with longevity when including published data with our meta-analysis (odds ratio = 1.17; p value = 1.85×10(-10)). We did not identify new genome-wide significant associations with longevity and did not replicate earlier findings except for APOE and FOXO3. Our inability to find new associations with survival to ages ≥90 years because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants.

MeSH Terms

• Aged
• Aged, 80 and over
• Apolipoproteins E
• Cell Adhesion Molecules
• Cohort Studies
• Female
• Forkhead Box Protein O3
• Forkhead Transcription Factors
• Genome-Wide Association Study
• Humans
• Longevity
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Receptors, Kainic Acid

Keywords

• APOE.
• FOXO3
• GWAS
• Longevity