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
18676988
TITLE
A high-density association screen of 155 ion transport genes for involvement with common migraine.
ABSTRACT
The clinical overlap between monogenic Familial Hemiplegic Migraine (FHM) and common migraine subtypes, and the fact that all three FHM genes are involved in the transport of ions, suggest that ion transport genes may underlie susceptibility to common forms of migraine. To test this leading hypothesis, we examined common variation in 155 ion transport genes using 5257 single nucleotide polymorphisms (SNPs) in a Finnish sample of 841 unrelated migraine with aura cases and 884 unrelated non-migraine controls. The top signals were then tested for replication in four independent migraine case-control samples from the Netherlands, Germany and Australia, totalling 2835 unrelated migraine cases and 2740 unrelated controls. SNPs within 12 genes (KCNB2, KCNQ3, CLIC5, ATP2C2, CACNA1E, CACNB2, KCNE2, KCNK12, KCNK2, KCNS3, SCN5A and SCN9A) with promising nominal association (0.00041 < P < 0.005) in the Finnish sample were selected for replication. Although no variant remained significant after adjusting for multiple testing nor produced consistent evidence for association across all cohorts, a significant epistatic interaction between KCNB2 SNP rs1431656 (chromosome 8q13.3) and CACNB2 SNP rs7076100 (chromosome 10p12.33) (pointwise P = 0.00002; global P = 0.02) was observed in the Finnish case-control sample. We conclude that common variants of moderate effect size in ion transport genes do not play a major role in susceptibility to common migraine within these European populations, although there is some evidence for epistatic interaction between potassium and calcium channel genes, KCNB2 and CACNB2. Multiple rare variants or trans-regulatory elements of these genes are not ruled out.
DATE PUBLISHED
2008 Nov 1
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2008/08/02
pubmed 2008/08/05 09:00
medline 2009/02/12 09:00
entrez 2008/08/05 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Nyholt DR Nyholt Dale R DR Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane4029, Queensland, Australia. dale.nyholt@qimr.edu.au
LaForge KS LaForge K Steven KS
Kallela M Kallela Mikko M
Alakurtti K Alakurtti Kirsi K
Anttila V Anttila Verneri V
Färkkilä M Färkkilä Markus M
Hämaläinen E Hämaläinen Eija E
Kaprio J Kaprio Jaakko J
Kaunisto MA Kaunisto Mari A MA
Heath AC Heath Andrew C AC
Montgomery GW Montgomery Grant W GW
Göbel H Göbel Hartmut H
Todt U Todt Unda U
Ferrari MD Ferrari Michel D MD
Launer LJ Launer Lenore J LJ
Frants RR Frants Rune R RR
Terwindt GM Terwindt Gisela M GM
de Vries B de Vries Boukje B
Verschuren WM Verschuren W M Monique WM
Brand J Brand Jan J
Freilinger T Freilinger Tobias T
Pfaffenrath V Pfaffenrath Volker V
Straube A Straube Andreas A
Ballinger DG Ballinger Dennis G DG
Zhan Y Zhan Yiping Y
Daly MJ Daly Mark J MJ
Cox DR Cox David R DR
Dichgans M Dichgans Martin M
van den Maagdenberg AM van den Maagdenberg Arn M J M AM
Kubisch C Kubisch Christian C
Martin NG Martin Nicholas G NG
Wessman M Wessman Maija M
Peltonen L Peltonen Leena L
Palotie A Palotie Aarno A
INVESTIGATORS
JOURNAL
VOLUME: 17
ISSUE: 21
TITLE: Human molecular genetics
ISOABBREVIATION: Hum. Mol. Genet.
YEAR: 2008
MONTH: Nov
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
089061 Wellcome Trust United Kingdom
089062 Wellcome Trust United Kingdom
AA007535 NIAAA NIH HHS United States
AA013320 NIAAA NIH HHS United States
AA013326 NIAAA NIH HHS United States
AA014041 NIAAA NIH HHS United States
AA07728 NIAAA NIH HHS United States
AA10249 NIAAA NIH HHS United States
AA11998 NIAAA NIH HHS United States
R01 NS37675 NINDS NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Aged
Aged, 80 and over
Case-Control Studies
Child
Demography
European Continental Ancestry Group genetics
Female genetics
Finland genetics
Gene Frequency genetics
Genes genetics
Genotype genetics
Humans genetics
Ion Transport genetics
Male genetics
Middle Aged genetics
Migraine without Aura genetics
Polymorphism, Single Nucleotide genetics
Young Adult genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC2566523 NLM
UKMS4366 NLM
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