eprintid: 1574474
rev_number: 35
eprint_status: archive
userid: 608
dir: disk0/01/57/44/74
datestamp: 2017-09-20 11:27:29
lastmod: 2022-01-25 23:32:38
status_changed: 2017-09-20 11:27:29
type: article
metadata_visibility: show
creators_name: Prins, BP
creators_name: Kuchenbaecker, KB
creators_name: Bao, Y
creators_name: Smart, M
creators_name: Zabaneh, D
creators_name: Fatemifar, G
creators_name: Luan, J
creators_name: Wareham, NJ
creators_name: Scott, RA
creators_name: Perry, JRB
creators_name: Langenberg, C
creators_name: Benzeval, M
creators_name: Kumari, M
creators_name: Zeggini, E
title: Genome-wide analysis of health-related biomarkers in the UK Household Longitudinal Study reveals novel associations
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D79
divisions: D12
divisions: G19
divisions: DD4
keywords: Genome-wide association studies, Heritable quantitative trait
note: © The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International
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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.
date: 2017-09-08
date_type: published
official_url: http://doi.org/10.1038/s41598-017-10812-1
oa_status: green
full_text_type: pub
pmcid: PMC5591265
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1421336
doi: 10.1038/s41598-017-10812-1
pii: 10.1038/s41598-017-10812-1
lyricists_name: Fatemifar, Ghazaleh
lyricists_name: Kuchenbaecker, Karoline
lyricists_name: Kumari, Meena
lyricists_id: GFATE12
lyricists_id: KBEKK98
lyricists_id: MKUMA95
actors_name: Bracey, Alan
actors_id: ABBRA90
actors_role: owner
full_text_status: public
publication: Scientific Reports
volume: 7
article_number: 11008
event_location: England
issn: 2045-2322
citation:        Prins, BP;    Kuchenbaecker, KB;    Bao, Y;    Smart, M;    Zabaneh, D;    Fatemifar, G;    Luan, J;                             ... Zeggini, E; + view all <#>        Prins, BP;  Kuchenbaecker, KB;  Bao, Y;  Smart, M;  Zabaneh, D;  Fatemifar, G;  Luan, J;  Wareham, NJ;  Scott, RA;  Perry, JRB;  Langenberg, C;  Benzeval, M;  Kumari, M;  Zeggini, E;   - view fewer <#>    (2017)    Genome-wide analysis of health-related biomarkers in the UK Household Longitudinal Study reveals novel associations.                   Scientific Reports , 7     , Article 11008.  10.1038/s41598-017-10812-1 <https://doi.org/10.1038/s41598-017-10812-1>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1574474/1/s41598-017-10812-1.pdf