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

Prins, Bram P and Kuchenbaecker, Karoline B and Bao, Yanchun and Smart, Melissa and Zabaneh, Delilah and Fatemifar, Ghazaleh and Luan, Jian an and Wareham, Nick J and Scott, Robert A and Perry, John RB and Langenberg, Claudia and Benzeval, Michaela and Kumari, Meena and Zeggini, Eleftheria (2017) 'Genome-wide analysis of health-related biomarkers in the UK Household Longitudinal Study reveals novel associations.' Scientific Reports, 7 (1). ISSN 2045-2322

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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.

Item Type: Article
Subjects: H Social Sciences > H Social Sciences (General)
R Medicine > R Medicine (General)
Divisions: Faculty of Science and Health > Mathematical Sciences, Department of
Faculty of Social Sciences > Institute for Social and Economic Research
Depositing User: Elements
Date Deposited: 26 Jun 2018 13:32
Last Modified: 02 Sep 2019 21:15
URI: http://repository.essex.ac.uk/id/eprint/21501

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