A study investigating the effects of common large DNA deletions and duplications has found no new links to complex disease. The research by the Wellcome Trust Case Consortium was published in Nature last week.
The multinational team compared the frequency of common duplications (termed Copy Number Variation or CNVs) in DNA from 16000 patients affected by complex diseases, such as rheumatoid arthritis and diabetes, to the DNA of 3000 controls (without disease). The Genome Wide Association Study (GWAS) found three CNVs associated with complex disease, but these were already known.
These results reveal a limited role for common CNVs in disease susceptibility. Previous studies have shown SNPs (single nucleotide polymorphisms) have a similarly limited role in disease susceptibility. Taken together, common CNVs and SNPs cannot account for the heritability of disease between generations.
The results beg the question: why do large changes in DNA such as CNVs not play a significant role in complex disease? In particular, large changes in DNA would be expected to have a greater impact on disease than a SNP. The authors state: 'Having completed these analyses the hypothesis that, a priori, an arbitrary common CNV is much more likely than an arbitrary common SNP to affect disease susceptibility is not supported by our data'.
The answer most likely comes from natural selection. For the CNV to be detected in the study, it must be common in the population. But highly detrimental changes in DNA are largely filtered out of the genome, meaning only CNVs and SNPs with small effects on disease susceptibility are common. Since there are far fewer CNVs than SNPs, the total contribution of CNVs to disease is - predictably - less.
Disappointing as these results are, they prompt the continued search for 'missing' heritability. Scientists are already examining rarer CNVs and SNPS, which are likely to have a larger effect on susceptibility to disease.