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Complex traits

Sequencing for disease architecture

Nature Reviews Genetics volume 14, page 518 (2013)Cite this article

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Morrison et al. sequenced the genomes of 962 individuals to an average depth of sixfold; this sample size and depth gives a high probability of identifying variants that have a frequency of >0.5%. Indeed, rare variants (those with a minor allele frequency of <1%) made up ~65% of the ~25 million variants identified in this study.

The authors grouped variants as 'rare', 'low-frequency' or 'common', and using a linear mixed model approach they assessed the contribution of variants within each group to the heritability of HDL-C levels. The data in this study suggests that common variants and rare variants account for 61.8% and 7.8%, respectively, of the variance in HDL-C levels. Along with results from previous studies, this finding suggests that many variants with small effects contribute to the genetic architecture of this trait. They also found that a few of the individuals with HDL-C levels in the tails of the distribution carried rare variants with large effects that had been previously identified in Mendelian conditions that affect lipoprotein levels.

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References

  1. Morrison, A. C. et al. Whole-genome sequence–based analysis of high-density lipoprotein cholesterol. Nature Genet. http://dx.doi.org/10.1038/ng.2671 (2013)

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Authors
  1. Mary Muers
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Goldstein, D. B. et al. Sequencing studies in human genetics: design and interpretation. Nature Rev. Genet. 14, 460–470 (2013)

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Muers, M. Sequencing for disease architecture. Nat Rev Genet 14, 518 (2013). https://doi.org/10.1038/nrg3533

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