A Genome-Wide Assessment of the Role of Untagged Copy Number Variants in Type 1 Diabetes

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For many complex traits, and in particular type 1 diabetes (T1D), the genome-wide association study (GWAS) design has been successful at detecting a large number of loci that contribute disease risk. However, in the case of T1D as well as almost all other traits, the sum of these loci does not fully explain the heritability estimated from familial studies. This observation raises the possibility that additional variants exist but have not yet been found because they have not effectively been targeted by the GWAS design. Here, we focus on a specific class of large deletions/duplications called copy number variants (CNVs), and more precisely to the subset of these loci that mutate rapidly, which are highly polymorphic. A consequence of this high level of polymorphism is that these variants have typically not been captured by previous GWAS studies. We use a family based design that is optimized to capture these previously untested variants. We then perform a genome-wide scan to assess their contribution to T1D. Our scan was technically successful but did not identify novel associations. This suggests that little was missed by the GWAS strategy, and that the remaining heritability of T1D is most likely driven by a large number of variants, either rare of common, but with a small individual contribution to disease risk.

Vyšlo v časopise: A Genome-Wide Assessment of the Role of Untagged Copy Number Variants in Type 1 Diabetes. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004367
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004367

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