Genome-wide analysis of health-related biomarkers in the UK Household Longitudinal Study reveals novel associations View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Bram P. Prins, Karoline B. Kuchenbaecker, Yanchun Bao, Melissa Smart, Delilah Zabaneh, Ghazaleh Fatemifar, Jian’an Luan, Nick J. Wareham, Robert A. Scott, John R. B. Perry, Claudia Langenberg, Michaela Benzeval, Meena Kumari, Eleftheria Zeggini

ABSTRACT

Serum biomarker levels are associated with the risk of complex diseases. Here, we aimed to gain insights into the genetic architecture of biomarker traits which can reflect health status. We performed genome-wide association analyses for twenty serum biomarkers involved in organ function and reproductive health. 9,961 individuals from the UK Household Longitudinal Study were genotyped using the Illumina HumanCoreExome array and variants imputed to the 1000 Genomes Project and UK10K haplotypes. We establish a polygenic heritability for all biomarkers, confirm associations of fifty-four established loci, and identify five novel, replicating associations at genome-wide significance. A low-frequency variant, rs28929474, (beta = 0.04, P = 2 × 10-10) was associated with levels of alanine transaminase, an indicator of liver damage. The variant is located in the gene encoding serine protease inhibitor, low levels of which are associated with alpha-1 antitrypsin deficiency which leads to liver disease. We identified novel associations (rs78900934, beta = 0.05, P = 6 × 10-12; rs2911280, beta = 0.09, P = 6 × 10-10) for dihydroepiandrosterone sulphate, a precursor to major sex-hormones, and for glycated haemoglobin (rs12819124, beta = -0.03, P = 4 × 10-9; rs761772, beta = 0.05, P = 5 × 10-9). rs12819124 is nominally associated with risk of type 2 diabetes. Our study offers insights into the genetic architecture of well-known and less well-studied biomarkers. More... »

PAGES

11008

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-017-10812-1

DOI

http://dx.doi.org/10.1038/s41598-017-10812-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1091478949

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28887542


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