The influence of rare variants in circulating metabolic biomarkers
Authors
Riveros-Mckay, Fernando
Oliver-Williams, Clare
Karthikeyan, Savita
Roberts, David
Di Angelantonio, Emanuele
Danesh, John
Zeggini, Eleftheria
Publication Date
2018-11-29Type
Webpages
Metadata
Show full item recordCitation
Riveros-Mckay, F., Oliver-Williams, C., Karthikeyan, S., Walter, K., Kundu, K., Ouwehand, W., Roberts, D., et al. (2018). The influence of rare variants in circulating metabolic biomarkers. [Webpages]. https://doi.org/10.1101/480699
Abstract
Abstract Circulating metabolite levels are biomarkers for cardiovascular disease (CVD). We tested association between rare sequence variants and 226 serum lipoproteins, lipids and amino acids in 7,142 healthy participants. Gene-based association analyses identified novel gene-trait associations with ACSL1 , MYCN , FBXO36 and B4GALNT3 ( p <2.5 × 10 −6 ), and confirmed established associations. Regulation of the pyruvate dehydrogenase (PDH) complex was associated for the first time, in gene set analyses, with IDL and LDL parameters, as well as circulating cholesterol ( p METASKAT <2.41 × 10 −6 ). Individuals at the lower tails of the distributions of four out of 49 lipoproteins and lipids had an excess of predicted deleterious variants in lipoprotein disorder and metabolism gene sets ( p permutation <0.00037). These four traits were CVD risk factors (e.g. S-VLDL-C), demonstrating that rare “protective” variation is a significant contributor to lipoprotein levels in a healthy population. In conclusion, rare variant analysis of these important metabolic biomarkers reveals novel loci and pathways involved in their regulation.
Embargo Lift Date
2100-01-01
Identifiers
External DOI: https://doi.org/10.1101/480699
This record's DOI: https://doi.org/10.17863/CAM.38473
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