Sunday, June 23, 2013

HDL-C heritability from whole genomes: common variants dominate

One of the advantages of whole genomes vs microarrays is that you can examine the impact of rare variants; in this study 25M variants (SNVs) were used as opposed to the usual 1M or so SNPs. The authors examine HDL-C level, which has heritability of 47-76%. They find that common variants account for almost all of the heritability, with rare variants (MAF < 1%) accounting for perhaps 10-20 percent as much as common variants.
Whole-genome sequence–based analysis of high-density lipoprotein cholesterol (Nature Genetics) (Supplement)

We describe initial steps for interrogating whole-genome sequence data to characterize the genetic architecture of a complex trait, levels of high-density lipoprotein cholesterol (HDL-C). We report whole-genome sequencing and analysis of 962 individuals from the Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE) studies. From this analysis, we estimate that common variation contributes more to heritability of HDL-C levels than rare variation, and screening for mendelian variants for dyslipidemia identified individuals with extreme HDL-C levels. Whole-genome sequencing analyses highlight the value of regulatory and non-protein-coding regions of the genome in addition to protein-coding regions.

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