Genomewide significant linkage to migrainous headache on chromosome 5q21

被引:76
作者
Nyholt, DR [1 ]
Morley, KI
Ferreira, MAR
Medland, SE
Boomsma, DI
Heath, AC
Merikangas, KR
Montgomery, GW
Martin, NG
机构
[1] Queensland Inst Med Res, PO Off Royal Brisbane Hosp, Brisbane, Qld 4029, Australia
[2] Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4067, Australia
[3] Univ Queensland, Dept Psychol, St Lucia, Qld 4067, Australia
[4] Free Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands
[5] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO USA
[6] NIMH, Sect Dev Genet Epidemiol, Intramural Res Program, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1086/444510
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Familial typical migraine is a common, complex disorder that shows strong familial aggregation. Using latent-class analysis (LCA), we identified subgroups of people with migraine/severe headache in a community sample of 12,245 Australian twins (60% female), drawn from two cohorts of individuals aged 23-90 years who completed an interview based on International Headache Society criteria. We report results from genomewide linkage analyses involving 756 twin families containing a total of 790 independent sib pairs ( 130 affected concordant, 324 discordant, and 336 unaffected concordant for LCA-derived migraine). Quantitative-trait linkage analysis produced evidence of significant linkage on chromosome 5q21 and suggestive linkage on chromosomes 8, 10, and 13. In addition, we replicated previously reported typical-migraine susceptibility loci on chromosomes 6p12.2-p21.1 and 1q21-q23, the latter being within 3 cM of the rare autosomal dominant familial hemiplegic migraine gene (ATP1A2), a finding which potentially implicates ATP1A2 in familial typical migraine for the first time. Linkage analyses of individual migraine symptoms for our six most interesting chromosomes provide tantalizing hints of the phenotypic and genetic complexity of migraine. Specifically, the chromosome 1 locus is most associated with phonophobia; the chromosome 5 peak is predominantly associated with pulsating headache; the chromosome 6 locus is associated with activity-prohibiting headache and photophobia; the chromosome 8 locus is associated with nausea/vomiting and moderate/severe headache; the chromosome 10 peak is most associated with phonophobia and photophobia; and the chromosome 13 peak is completely due to association with photophobia. These results will prove to be invaluable in the design and analysis of future linkage and linkage disequilibrium studies of migraine.
引用
收藏
页码:500 / 512
页数:13
相关论文
共 80 条
[1]   Merlin-rapid analysis of dense genetic maps using sparse gene flow trees [J].
Abecasis, GR ;
Cherny, SS ;
Cookson, WO ;
Cardon, LR .
NATURE GENETICS, 2002, 30 (01) :97-101
[2]   GRR: graphical representation of relationship errors [J].
Abecasis, GR ;
Cherny, SS ;
Cookson, WOC ;
Cardon, LR .
BIOINFORMATICS, 2001, 17 (08) :742-743
[3]   Multipoint quantitative-trait linkage analysis in general pedigrees [J].
Almasy, L ;
Blangero, J .
AMERICAN JOURNAL OF HUMAN GENETICS, 1998, 62 (05) :1198-1211
[4]   Localization of a gene for migraine without aura to chromosome 4q21 [J].
Björnsson, A ;
Gudmundsson, G ;
Gudfinnsson, E ;
Hrafnsdóttir, M ;
Benedikz, J ;
Skúladóttir, S ;
Kristjánsson, K ;
Frigge, ML ;
Kong, A ;
Stefánsson, K ;
Gulcher, JR .
AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 73 (05) :986-993
[5]   Significant linkage to migraine with aura on chromosome 11q24 [J].
Cader, ZM ;
Noble-Topham, S ;
Dyment, DA ;
Cherny, SS ;
Brown, JD ;
Rice, GPA ;
Ebers, GC .
HUMAN MOLECULAR GENETICS, 2003, 12 (19) :2511-2517
[6]   Identification of a susceptibility locus for migraine with and without aura on 6p12.2-p21.1 [J].
Carlsson, A ;
Forsgren, L ;
Nylander, PO ;
Hellman, U ;
Forsman-Semb, K ;
Holmgren, G ;
Holmberg, D ;
Holmberg, M .
NEUROLOGY, 2002, 59 (11) :1804-1807
[7]   A simple correction for multiple comparisons in interval mapping genome scans [J].
Cheverud, JM .
HEREDITY, 2001, 87 (1) :52-58
[8]   Investigation of hormone receptor genes in migraine [J].
Colson, NJ ;
Lea, RA ;
Quinlan, S ;
MacMillan, J ;
Griffiths, LR .
NEUROGENETICS, 2005, 6 (01) :17-23
[9]   The estrogen receptor 1 G594A polymorphism is associated with migraine susceptibility in two independent case/control groups [J].
Colson, NJ ;
Lea, RA ;
Quinlan, S ;
MacMillan, J ;
Griffiths, LR .
NEUROGENETICS, 2004, 5 (02) :129-133
[10]   Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump α2 subunit associated with familial hemiplegic migraine type 2 [J].
De Fusco, M ;
Marconi, R ;
Silvestri, L ;
Atorino, L ;
Rampoldi, L ;
Morgante, L ;
Ballabio, A ;
Aridon, P ;
Casari, G .
NATURE GENETICS, 2003, 33 (02) :192-196