Genetic Epidemiology, Translational Neurogenomics, Psychiatric 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
21862451
TITLE
GWAS of butyrylcholinesterase activity identifies four novel loci, independent effects within BCHE and secondary associations with metabolic risk factors.
ABSTRACT
Serum butyrylcholinesterase (BCHE) activity is associated with obesity, blood pressure and biomarkers of cardiovascular and diabetes risk. We have conducted a genome-wide association scan to discover genetic variants affecting BCHE activity, and to clarify whether the associations between BCHE activity and cardiometabolic risk factors are caused by variation in BCHE or whether BCHE variation is secondary to the metabolic abnormalities. We measured serum BCHE in adolescents and adults from three cohorts of Australian twin and family studies. The genotypes from ∼2.4 million single-nucleotide polymorphisms (SNPs) were available in 8791 participants with BCHE measurements. We detected significant associations with BCHE activity at three independent groups of SNPs at the BCHE locus (P = 5.8 × 10(-262), 7.8 × 10(-47), 2.9 × 10(-12)) and at four other loci: RNPEP (P = 9.4 × 10(-16)), RAPH1-ABI2 (P = 4.1 × 10(-18)), UGT1A1 (P = 4.0 × 10(-8)) and an intergenic region on chromosome 8 (P = 1.4 × 10(-8)). These loci affecting BCHE activity were not associated with metabolic risk factors. On the other hand, SNPs in genes previously associated with metabolic risk had effects on BCHE activity more often than can be explained by chance. In particular, SNPs within FTO and GCKR were associated with BCHE activity, but their effects were partly mediated by body mass index and triglycerides, respectively. We conclude that variation in BCHE activity is due to multiple variants across the spectrum from uncommon/large effect to common/small effect, and partly results from (rather than causes) metabolic abnormalities.
DATE PUBLISHED
2011 Nov 15
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2011/08/23
aheadofprint 2011/09/06
entrez 2011/08/25 06:00
pubmed 2011/08/25 06:00
medline 2012/05/16 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Benyamin B Benyamin Beben B Queensland Institute of Medical Research, Brisbane 4006, Australia.
Middelberg RP Middelberg Rita P RP
Lind PA Lind Penelope A PA
Valle AM Valle Anne M AM
Gordon S Gordon Scott S
Nyholt DR Nyholt Dale R DR
Medland SE Medland Sarah E SE
Henders AK Henders Anjali K AK
Heath AC Heath Andrew C AC
Madden PA Madden Pamela A F PA
Visscher PM Visscher Peter M PM
O'Connor DT O'Connor Daniel T DT
Montgomery GW Montgomery Grant W GW
Martin NG Martin Nicholas G NG
Whitfield JB Whitfield John B JB
INVESTIGATORS
JOURNAL
VOLUME: 20
ISSUE: 22
TITLE: Human molecular genetics
ISOABBREVIATION: Hum. Mol. Genet.
YEAR: 2011
MONTH: Nov
DAY: 15
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
AA07535 NIAAA NIH HHS United States
AA10248 NIAAA NIH HHS United States
AA11998 NIAAA NIH HHS United States
AA13320 NIAAA NIH HHS United States
AA13321 NIAAA NIH HHS United States
AA13326 NIAAA NIH HHS United States
AA14041 NIAAA NIH HHS United States
AA17688 NIAAA NIH HHS United States
DA12854 NIDA NIH HHS United States
K05 AA017688 NIAAA NIH HHS United States
MH66206 NIMH NIH HHS United States
P42-ES010337 NIEHS NIH HHS United States
R37-GM18360 NIGMS NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adaptor Proteins, Signal Transducing genetics
Adolescent genetics
Adult genetics
Aminopeptidases genetics
Butyrylcholinesterase genetics
Carrier Proteins genetics
Female genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study methods
Genotype methods
Glucuronosyltransferase genetics
Humans genetics
Male genetics
Membrane Proteins genetics
Polymorphism, Single Nucleotide genetics
Proteins genetics
Risk Factors genetics
Young Adult genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Adaptor Proteins, Signal Transducing
0 Carrier Proteins
0 FTO protein, human
0 GCKR protein, human
0 Membrane Proteins
0 Proteins
0 RAPH1 protein, human
EC 2.4.1.- UGT1A1 enzyme
EC 2.4.1.17 Glucuronosyltransferase
EC 3.1.1.- Butyrylcholinesterase
EC 3.4.11.- Aminopeptidases
EC 3.4.11.6 aminopeptidase B
OTHER ID's
OTHERID SOURCE
PMC3196893 NLM