Copy number variation is a type of genetic difference between individuals in which a section of DNA, usually one that is already duplicated multiple times in most people, has a different number of repeats. Researchers have studied copy number variation and relationships with longevity, both in general, in the sense of looking for correlations, and in specific, looking at copy number variations in a single gene. As is the case for most genetic correlations in the matter of human longevity, the vast majority of results suggest only tiny effects on mortality and fail to reproduce between study populations. That tells us that most naturally occurring individual genetic contributions to longevity are both small and highly conditional. The study here is representative of the type, and thus I would say that there is no great expectation that the results will be replicated in other data sets.
Human lifespan has long been observed as a complex trait with approximately 25% genetic contributions. To date, only very few genes have been shown consistently associated with it. Recent studies reported that copy number variation (CNV) may directly contribute to human lifespan. CNV is a general term for all the chromosomal rearrangements, such as deletions, duplications. CNVs can change gene structures, thus affecting gene expression and phenotypes. In human, CNVs have been implicated in numerous diseases, such as autism and diabetes. CNVs also contribute significantly to the genome instability of cancer cells.
A few studies have investigated the association of CNV with human lifespan using genome-wide approaches. One reported this association in 11442 human samples representing two cohorts. They found large deletions in 11p15.5 among the oldest people. Another study uncovered a deletion in the CNTNAP4 gene in a female group of 80 years of age, but not the male group. Recently, a study in Caucasians revealed an insertion allele of the CNTNAP2 gene in esv11910 CNV of males, but not females.
In this study, we investigated the association of CNVs and longevity in Han Chinese by genotyping 4007 individuals obtained from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) database. We have identified a few CNVs, and most of them were new. These CNV regions encode nineteen known genes, and some of which have been shown to affect aging-related phenotypes such as the shortening of telomere length (ZNF208), the risk of cancer (FOXA1, LAMA5, ZNF716), and vascular and immune-related diseases (ARHGEF10, TOR2A, SH2D3C). In addition, we found several pathways enriched in long-lived genomes, including FOXA1 and FOXA transcription factor networks involved in regulating aging or age-dependent diseases such as cancer.