Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
25820613
TITLE
Genome-wide association study of blood lead shows multiple associations near ALAD.
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.
The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
DATE PUBLISHED
2015 Jul 1
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2014/11/16
accepted 2015/03/24
aheadofprint 2015/03/27
entrez 2015/03/31 06:00
pubmed 2015/03/31 06:00
medline 2015/03/31 06:00
pmc-release 2016/07/01 00:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Warrington NM Warrington Nicole M NM University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
Zhu G Zhu Gu G QIMR Berghofer Medical Research Institute, Locked Bag 2000, Royal Brisbane Hospital, Queensland 4029, Australia.
Dy V Dy Veronica V Royal Prince Alfred Hospital, Sydney, Australia.
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
Madden PA Madden Pamela A F PA Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
Hemani G Hemani Gibran G MRC Integrative Epidemiology Unit, School of Social and Community Medicine and.
Kemp JP Kemp John P JP University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia, MRC Integrative Epidemiology Unit, School of Social and Community Medicine and.
Mcmahon G Mcmahon George G MRC Integrative Epidemiology Unit, School of Social and Community Medicine and.
St Pourcain B St Pourcain Beate B School of Social and Community Medicine and.
Timpson NJ Timpson Nicholas J NJ MRC Integrative Epidemiology Unit, School of Social and Community Medicine and.
Taylor CM Taylor Caroline M CM Centre for Child and Adolescent Health, School of Social and Community Medicine, University of Bristol, Bristol, UK.
Golding J Golding Jean J School of Social and Community Medicine and.
Lawlor DA Lawlor Debbie A DA MRC Integrative Epidemiology Unit, School of Social and Community Medicine and.
Steer C Steer Colin C Centre for Child and Adolescent Health, School of Social and Community Medicine, University of Bristol, Bristol, UK.
Montgomery GW Montgomery Grant W GW QIMR Berghofer Medical Research Institute, Locked Bag 2000, Royal Brisbane Hospital, Queensland 4029, Australia.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Locked Bag 2000, Royal Brisbane Hospital, Queensland 4029, Australia.
Davey Smith G Davey Smith George G MRC Integrative Epidemiology Unit, School of Social and Community Medicine and.
Evans DM Evans David M DM University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia, MRC Integrative Epidemiology Unit, School of Social and Community Medicine and.
Whitfield JB Whitfield John B JB QIMR Berghofer Medical Research Institute, Locked Bag 2000, Royal Brisbane Hospital, Queensland 4029, Australia, John.Whitfield@qimrberghofer.edu.au.
INVESTIGATORS
JOURNAL
VOLUME: 24
ISSUE: 13
TITLE: Human molecular genetics
ISOABBREVIATION: Hum. Mol. Genet.
YEAR: 2015
MONTH: Jul
DAY: 1
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1460-2083
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Hum Mol Genet
COUNTRY: England
ISSNLINKING: 0964-6906
NLMUNIQUEID: 9208958
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
AA007535 NIAAA NIH HHS United States
AA013320 NIAAA NIH HHS United States
AA013321 NIAAA NIH HHS United States
AA013326 NIAAA NIH HHS United States
AA014041 NIAAA NIH HHS United States
DA012854 NIDA NIH HHS United States
MC_PC_15018 Medical Research Council United Kingdom
MC_UU_12013/1 Medical Research Council United Kingdom
MC_UU_12013/3 Medical Research Council United Kingdom
MC_UU_12013/4 Medical Research Council United Kingdom
MC_UU_12013/5 Medical Research Council United Kingdom
WT088806 Wellcome Trust United Kingdom
GENERAL NOTE
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OTHER ID's
OTHERID SOURCE
PMC4459389 [Available on 07/01/16] NLM