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
21598361
TITLE
LPAR1 and ITGA4 regulate peripheral blood monocyte counts.
ABSTRACT
We recently mapped a quantitative trait locus for monocyte counts to chromosome 9q31 (rs7023923). Here we extend this work by showing with two independent approaches that rs7023923 regulates the expression levels of the nearby LPAR1 gene (P<0.0001), specifically implicating this gene in monocyte development. Furthermore, we tested 10 additional loci identified in the original analysis for replication in 1,122 individuals and confirm that rs6740847 near the alpha-4-integrin gene (ITGA4) associates with variation in monocyte counts (combined P=2.7×10(-10)). This variant is in complete linkage disequilibrium (r(2) =1) with a previously reported eQTL for ITGA4 (rs2124440), indicating that this is the likely causal gene in the region. Our results indicate that rs7023923 and rs6740847 respectively upregulate LPAR1 and downregulate ITGA4 expression and this increases the number of monocytes circulating in the peripheral blood. Further studies that investigate the downstream mechanism involved and the impact on immune function are warranted.
2011 Wiley-Liss, Inc.
DATE PUBLISHED
2011 Aug
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2011/04/12
accepted 2011/04/29
aheadofprint 2011/07/12
entrez 2011/05/21 06:00
pubmed 2011/05/21 06:00
medline 2011/12/14 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Maugeri N Maugeri Narelle N Queensland Institute of Medical Research, Brisbane, Australia.
Powell JE Powell Joseph E JE
't Hoen PA 't Hoen Peter A C PA
de Geus EJ de Geus Eco J C EJ
Willemsen G Willemsen Gonneke G
Kattenberg M Kattenberg Mathijs M
Henders AK Henders Anjali K AK
Wallace L Wallace Leanne L
Penninx B Penninx Brenda B
Hottenga JJ Hottenga Jouke-Jan JJ
Medland SE Medland Sarah E SE
Saviouk V Saviouk Viatcheslav V
Martin NG Martin Nicholas G NG
Visscher PM Visscher Peter M PM
van Ommen GJ van Ommen Gert-Jan B GJ
Frazer IH Frazer Ian H IH
Boomsma DI Boomsma Dorret I DI
Montgomery GW Montgomery Grant W GW
Ferreira MA Ferreira Manuel A R MA
INVESTIGATORS
JOURNAL
VOLUME: 32
ISSUE: 8
TITLE: Human mutation
ISOABBREVIATION: Hum. Mutat.
YEAR: 2011
MONTH: Aug
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1098-1004
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Hum Mutat
COUNTRY: United States
ISSNLINKING: 1059-7794
NLMUNIQUEID: 9215429
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
R01D0042157-01A PHS HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Chromosome Mapping
Gene Expression Profiling
Gene Expression Regulation
Genotype
Humans
Integrin alpha4 metabolism
Leukocyte Count metabolism
Monocytes metabolism
Polymorphism, Single Nucleotide metabolism
Quantitative Trait Loci genetics
Receptors, Lysophosphatidic Acid metabolism
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Receptors, Lysophosphatidic Acid
143198-26-9 Integrin alpha4
OTHER ID's