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Variation across the allele frequency spectrum

Nature Genetics volume 42, pages 648–650 (2010)Cite this article

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A new study finds that individuals with high plasma triglyceride levels carry approximately twice as many rare, coding genetic variants within four candidate genes identified through genome-wide association studies than individuals without these high levels. This study demonstrates the overlap of rare and common variant signals at loci associated with lipid levels and shows the value of efforts to extend susceptibility variant discovery to embrace the full allele-frequency spectrum.

Common-variant genome-wide association studies (GWAS) have, in recent years, been responsible for substantial advances in dissecting the genetic basis of common disease. However, for many of these traits, much of the genetic variation influencing individual risk of disease remains unexplained1, and discovery efforts are now increasingly focused on sources of genetic variation poorly captured by existing GWAS approaches. One clear target of these new approaches, powered by the availability of next-generation sequencing technologies, lies in enumerating the contribution to phenotypic variation made by low-frequency (minor allele frequencies in the 0.3–5.0% range) and rare (minor allele frequencies below 0.3%) genetic variants1. On page 684 of this issue, Robert Hegele and colleagues combine these approaches by resequencing within associated loci from a GWAS for high triglyceride levels. By demonstrating that both common and low-frequency alleles at these loci are associated with levels of circulating triglycerides, this study provides important clues to the architecture of variants influencing common biomedical traits2.

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Figure 1: Genetic susceptibility variants across the allele frequency spectrum.

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  1. Anna L. Gloyn and Mark I. McCarthy are at the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.,

    Anna L Gloyn & Mark I McCarthy

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  1. Anna L Gloyn
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  2. Mark I McCarthy
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Correspondence to Mark I McCarthy.

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Gloyn, A., McCarthy, M. Variation across the allele frequency spectrum. Nat Genet 42, 648–650 (2010). https://doi.org/10.1038/ng0810-648

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