Genome-wide association study of blood lead shows multiple associations near ALAD

Warrington, Nicole M., Zhu, Gu, Dy, Veronica, Heath, Andrew C., Madden, Pamela A. F., Hemani, Gibran, Kemp, John P., Mcmahon, George, St Pourcain, Beate, Timpson, Nicholas J., Taylor, Caroline M., Golding, Jean, Lawlor, Debbie A., Steer, Colin, Montgomery, Grant W., Martin, Nicholas G., Smith, George Davey, Evans, David M. and Whitfield, John B. (2015) Genome-wide association study of blood lead shows multiple associations near ALAD. Human Molecular Genetics, 24 13: 3871-3879. doi:10.1093/hmg/ddv112


Author Warrington, Nicole M.
Zhu, Gu
Dy, Veronica
Heath, Andrew C.
Madden, Pamela A. F.
Hemani, Gibran
Kemp, John P.
Mcmahon, George
St Pourcain, Beate
Timpson, Nicholas J.
Taylor, Caroline M.
Golding, Jean
Lawlor, Debbie A.
Steer, Colin
Montgomery, Grant W.
Martin, Nicholas G.
Smith, George Davey
Evans, David M.
Whitfield, John B.
Title Genome-wide association study of blood lead shows multiple associations near ALAD
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
1460-2083
Publication date 2015-03-27
Year available 2015
Sub-type Article (original research)
DOI 10.1093/hmg/ddv112
Volume 24
Issue 13
Start page 3871
End page 3879
Total pages 9
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2016
Language eng
Formatted abstract
Exposure to high levels of environmental lead, or biomarker evidence of high body lead content, is associated with anaemia, developmental and neurological deficits in children, and increased mortality in adults. Adverse effects of lead still occur despite substantial reduction in environmental exposure. There is genetic variation between individuals in blood lead concentration but the polymorphisms contributing to this have not been defined. We measured blood or erythrocyte lead content, and carried out genome-wide association analysis, on population-based cohorts of adult volunteers from Australia and UK (N = 5433). Samples from Australia were collected in two studies, in 1993-1996 and 2002-2005 and from UK in 1991-1992. One locus, at ALAD on chromosome 9, showed consistent association with blood lead across countries and evidence for multiple independent allelic effects. The most significant single nucleotide polymorphism (SNP), rs1805313 (P = 3.91 * 10(-14) for lead concentration in a meta-analysis of all data), is known to have effects on ALAD expression in blood cells but other SNPs affecting ALAD expression did not affect blood lead. Variants at 12 other loci, including ABO, showed suggestive associations (5 * 10(-6) > P > 5 * 10(-8)). Identification of genetic polymorphisms affecting blood lead reinforces the view that genetic factors, as well as environmental ones, are important in determining blood lead levels. The ways in which ALAD variation affects lead uptake or distribution are still to be determined.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
UQ Diamantina Institute Publications
 
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Created: Thu, 16 Jul 2015, 12:46:26 EST by Nicole Warrington on behalf of UQ Diamantina Institute