Projects per year
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.
Original language | English |
---|---|
Pages (from-to) | 3871–3879 |
Number of pages | 9 |
Journal | Human Molecular Genetics |
Volume | 24 |
Issue number | 13 |
DOIs | |
Publication status | Published - 1 Jul 2015 |
Bibliographical note
© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].Fingerprint
Dive into the research topics of 'Genome-wide association study of blood lead shows multiple associations near ALAD'. Together they form a unique fingerprint.Projects
- 3 Finished
-
MRC UoB UNITE Unit - Programme 1
Davey Smith, G. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research
-
MRC UoB UNITE Unit - Programme 5
Lawlor, D. A. (Principal Investigator) & Lawlor, D. A. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research
-
MRC UoB UNITE Unit - programme 3
Timpson, N. J. (Principal Investigator) & Timpson, N. J. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research
Profiles
-
Dr Caroline M Taylor
- Bristol Medical School (PHS) - Associate Professor in Nutrition
- Bristol Population Health Science Institute
Person: Academic , Member