Trait components provide tools to dissect the genetic susceptibility of migraine

Show full item record



Permalink

http://hdl.handle.net/10138/298457

Citation

Anttila , V , Kallela , M , Oswell , G , Kaunisto , M , Nyholt , D R , Hämäläinen , E , Havanka , H , Ilmavirta , M , Terwilliger , J , Sobel , E , Peltonen , L , Kaprio , J , Färkkilä , M , Wessman , M & Palotie , A 2006 , ' Trait components provide tools to dissect the genetic susceptibility of migraine ' , American Journal of Human Genetics , vol. 79 , no. 1 , pp. 85-99 .

Title: Trait components provide tools to dissect the genetic susceptibility of migraine
Author: Anttila, Verneri; Kallela, Mikko; Oswell, Greg; Kaunisto, Mari; Nyholt, Dale R; Hämäläinen, Eija; Havanka, Hannele; Ilmavirta, Matti; Terwilliger, Joseph; Sobel, Eric; Peltonen, Leena; Kaprio, Jaakko; Färkkilä, Markus; Wessman, Maija; Palotie, Aarno
Contributor organization: Finnish Genome Center (-2009)
Neurologian yksikkö
Kliinisen kemian yksikkö (-2009)
Research Programs (Faculty of Medicine) (-2009)
Department of Medical and Clinical Genetics
Department of Public Health
Research Programme of Molecular Medicine
Genetic Epidemiology
Date: 2006
Language: eng
Number of pages: 15
Belongs to series: American Journal of Human Genetics
ISSN: 0002-9297
URI: http://hdl.handle.net/10138/298457
Abstract: "The commonly used ""end diagnosis"" phenotype that is adopted in linkage and association studies of complex traits is likely to represent an oversimplified model of the genetic background of a disease. This is also likely to be the case for common types of migraine, for which no convincingly associated genetic variants have been reported. In headache disorders, most genetic studies have used end diagnoses of the International Headache Society ( IHS) classification as phenotypes. Here, we introduce an alternative strategy; we use trait components-individual clinical symptoms of migraine-to determine affection status in genomewide linkage analyses of migraine-affected families. We identified linkage between several traits and markers on chromosome 4q24 ( highest LOD score under locus heterogeneity [ HLOD] 4.52), a locus we previously reported to be linked to the end diagnosis migraine with aura. The pulsation trait identified a novel locus on 17p13 ( HLOD 4.65). Additionally, a trait combination phenotype ( IHS full criteria) revealed a locus on 18q12 ( HLOD 3.29), and the age at onset trait revealed a locus on 4q28 ( HLOD 2.99). Furthermore, suggestive or nearly suggestive evidence of linkage to four additional loci was observed with the traits phonophobia ( 10q22) and aggravation by physical exercise ( 12q21, 15q14, and Xp21), and, interestingly, these loci have been linked to migraine in previous studies. Our findings suggest that the use of symptom components of migraine instead of the end diagnosis provides a useful tool in stratifying the sample for genetic studies.""The commonly used ""end diagnosis"" phenotype that is adopted in linkage and association studies of complex traits is likely to represent an oversimplified model of the genetic background of a disease. This is also likely to be the case for common types of migraine, for which no convincingly associated genetic variants have been reported. In headache disorders, most genetic studies have used end diagnoses of the International Headache Society ( IHS) classification as phenotypes. Here, we introduce an alternative strategy; we use trait components-individual clinical symptoms of migraine-to determine affection status in genomewide linkage analyses of migraine-affected families. We identified linkage between several traits and markers on chromosome 4q24 ( highest LOD score under locus heterogeneity [ HLOD] 4.52), a locus we previously reported to be linked to the end diagnosis migraine with aura. The pulsation trait identified a novel locus on 17p13 ( HLOD 4.65). Additionally, a trait combination phenotype ( IHS full criteria) revealed a locus on 18q12 ( HLOD 3.29), and the age at onset trait revealed a locus on 4q28 ( HLOD 2.99). Furthermore, suggestive or nearly suggestive evidence of linkage to four additional loci was observed with the traits phonophobia ( 10q22) and aggravation by physical exercise ( 12q21, 15q14, and Xp21), and, interestingly, these loci have been linked to migraine in previous studies. Our findings suggest that the use of symptom components of migraine instead of the end diagnosis provides a useful tool in stratifying the sample for genetic studies.""The commonly used ""end diagnosis"" phenotype that is adopted in linkage and association studies of complex traits is likely to represent an oversimplified model of the genetic background of a disease. This is also likely to be the case for common types of migraine, for which no convincingly associated genetic variants have been reported. In headache disorders, most genetic studies have used end diagnoses of the International Headache Society ( IHS) classification as phenotypes. Here, we introduce an alternative strategy; we use trait components-individual clinical symptoms of migraine-to determine affection status in genomewide linkage analyses of migraine-affected families. We identified linkage between several traits and markers on chromosome 4q24 ( highest LOD score under locus heterogeneity [ HLOD] 4.52), a locus we previously reported to be linked to the end diagnosis migraine with aura. The pulsation trait identified a novel locus on 17p13 ( HLOD 4.65). Additionally, a trait combination phenotype ( IHS full criteria) revealed a locus on 18q12 ( HLOD 3.29), and the age at onset trait revealed a locus on 4q28 ( HLOD 2.99). Furthermore, suggestive or nearly suggestive evidence of linkage to four additional loci was observed with the traits phonophobia ( 10q22) and aggravation by physical exercise ( 12q21, 15q14, and Xp21), and, interestingly, these loci have been linked to migraine in previous studies. Our findings suggest that the use of symptom components of migraine instead of the end diagnosis provides a useful tool in stratifying the sample for genetic studies."
Subject: 314 Health sciences
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion


Files in this item

Total number of downloads: Loading...

Files Size Format View
untitled.pdf 3.302Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record