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
19084217
TITLE
Variants in TF and HFE explain approximately 40% of genetic variation in serum-transferrin levels.
ABSTRACT
Only a small proportion of genetic variation in complex traits has been explained by SNPs from genome-wide association studies (GWASs). We report the results from two GWASs for serum markers of iron status (serum iron, serum transferrin, transferrin saturation with iron, and serum ferritin), which are important in iron overload (e.g., hemochromatosis) and deficiency (e.g., anemia) conditions. We performed two GWASs on samples of Australians of European descent. In the first GWAS, 411 adolescent twins and their siblings were genotyped with 100K SNPs. rs1830084, 10.8 kb 3' of TF, was significantly associated with serum transferrin (p total association test = 1.0 x 10(-9); p within-family test = 2.2 x 10(-5)). In the second GWAS on an independent sample of 459 female monozygotic (MZ) twin pairs genotyped with 300K SNPs, we found rs3811647 (within intron 11 of TF, HapMap CEU r(2) with rs1830084 = 0.86) was significantly associated with serum transferrin (p = 3.0 x 10(-15)). In the second GWAS, we found two additional and independent SNPs on TF (rs1799852 and rs2280673) and confirmed the known C282Y mutation in HFE to be independently associated with serum transferrin. The three variants in TF (rs3811647, rs1799852 and rs2280673) plus the HFE C282Y mutation explained approximately 40% of genetic variation in serum transferrin (p = 7.8 x 10(-25)). These findings are potentially important for our understanding of iron metabolism and of regulation of hepatic protein secretion, and also strongly support the hypothesis that the genetic architecture of some endophenotypes may be simpler than that of disease.
DATE PUBLISHED
2009 Jan
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2008/09/13
revised 2008/11/13
accepted 2008/11/20
aheadofprint 2008/12/11
entrez 2008/12/17 09:00
pubmed 2008/12/17 09:00
medline 2009/02/06 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Benyamin B Benyamin Beben B Queensland Institute of Medical Research, Brisbane 4029, Australia. bebenb@qimr.edu.au
McRae AF McRae Allan F AF
Zhu G Zhu Gu G
Gordon S Gordon Scott S
Henders AK Henders Anjali K AK
Palotie A Palotie Aarno A
Peltonen L Peltonen Leena L
Martin NG Martin Nicholas G NG
Montgomery GW Montgomery Grant W GW
Whitfield JB Whitfield John B JB
Visscher PM Visscher Peter M PM
INVESTIGATORS
JOURNAL
VOLUME: 84
ISSUE: 1
TITLE: American journal of human genetics
ISOABBREVIATION: Am. J. Hum. Genet.
YEAR: 2009
MONTH: Jan
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1537-6605
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Am J Hum Genet
COUNTRY: United States
ISSNLINKING: 0002-9297
NLMUNIQUEID: 0370475
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Aged
Aged, 80 and over
Anemia, Iron-Deficiency metabolism
Australia epidemiology
Child epidemiology
Europe ethnology
Female ethnology
Genetic Variation ethnology
Genome-Wide Association Study ethnology
Hemochromatosis metabolism
Histocompatibility Antigens Class I genetics
Humans genetics
Iron blood
Male blood
Membrane Proteins genetics
Middle Aged genetics
Polymorphism, Single Nucleotide genetics
Transferrin genetics
Young Adult genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 HFE protein, human
0 Histocompatibility Antigens Class I
0 Membrane Proteins
0 Transferrin
E1UOL152H7 Iron
OTHER ID's
OTHERID SOURCE
PMC2668053 NLM