You are here: Home Publications Genome-wide association study of blood lead shows multiple associations near ALAD

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

Warrington, N. M., Zhu, G., Dy, V., Heath, A. C., Madden, P. A. F., Hemani, G., Kemp, J. P., McMahon, G., St Pourcain, B., Timpson, N. J., Taylor, C. M., Golding, J., Lawlor, D. A., Steer, C., Montgomery, G. W., Martin, N. G., Smith, G. D., Evans, D. M., & Whitfield, J. 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.
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.
About MPI

This is the MPI

The Max Planck Institute for Psycholinguistics is an institute of the German Max Planck Society. Our mission is to undertake basic research into the psychological,social and biological foundations of language. The goal is to understand how our minds and brains process language, how language interacts with other aspects of mind, and how we can learn languages of quite different types.

The institute is situated on the campus of the Radboud University. We participate in the Donders Institute for Brain, Cognition and Behaviour, and have particularly close ties to that institute's Centre for Cognitive Neuroimaging. We also participate in the Centre for Language Studies. A joint graduate school, the IMPRS in Language Sciences, links the Donders Institute, the CLS and the MPI.

 

Street address
Wundtlaan 1
6525 XD Nijmegen
The Netherlands


Mailing address
P.O. Box 310
6500 AH Nijmegen
The Netherlands

Phone:   +31-24-3521911
Fax:        +31-24-3521213
E-mail:   


Public Outreach Officer
Charlotte Horn