Rxivist logo

Deep-coverage whole genome sequencing at the population level is now feasible and offers potential advantages for locus discovery, particularly in the analysis rare mutations in non-coding regions. Here, we performed whole genome sequencing in 16,324 participants from four ancestries at mean depth >29X and analyzed correlations of genotypes with four quantitative traits - plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. We conducted a discovery analysis including common or rare variants in coding as well as non-coding regions and developed a framework to interpret genome sequence for dyslipidemia risk. Common variant association yielded loci previously described with the exception of a few variants not captured earlier by arrays or imputation. In coding sequence, rare variant association yielded known Mendelian dyslipidemia genes and, in non-coding sequence, we detected no rare variant association signals after application of four approaches to aggregate variants in non-coding regions. We developed a new, genome-wide polygenic score for LDL-C and observed that a high polygenic score conferred similar effect size to a monogenic mutation (~30 mg/dl higher LDL-C for each); however, among those with extremely high LDL-C, a high polygenic score was considerably more prevalent than a monogenic mutation (23% versus 2% of participants, respectively).

Download data

  • Downloaded 2,053 times
  • Download rankings, all-time:
    • Site-wide: 3,495 out of 89,274
    • In genomics: 633 out of 5,695
  • Year to date:
    • Site-wide: 66,790 out of 89,274
  • Since beginning of last month:
    • Site-wide: 47,386 out of 89,274

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News