Abstract
| Original language | English |
|---|---|
| Journal | American Journal of Human Genetics |
| Volume | 82 |
| Issue number | 5 |
| Pages (from-to) | 1051-1063 |
| Number of pages | 13 |
| ISSN | 0002-9297 |
| DOIs | |
| Publication status | Published - 2008 |
| MoE publication type | A1 Journal article-refereed |
Fields of Science
- FAMILIAL HEMIPLEGIC MIGRAINE
- GENOME-WIDE ASSOCIATION
- LINKAGE ANALYSIS
- SUSCEPTIBILITY LOCUS
- COMPLEX TRAITS
- MACULAR DEGENERATION
- MULTIPLE-SCLEROSIS
- GENETIC DISSECTION
- PROSTATE-CANCER
- INFLUENCES RISK
Cite this
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Consistently replicating locus linked to migraine on 10q22-q23. / Anttila, Verneri; Nyholt, Dale R; Kallela, Mikko; Artto, Ville; Vepsäläinen, Salli; Jakkula, Eveliina; Wennerström, Annika; Tikka-Kleemola, Päivi; Kaunisto, Mari A; Hämäläinen, Eija; Widen, Elisabeth; Terwilliger, Joseph; Merikangas, Kathleen; Montgomery, Grant W; Martin, Nicholas G; Daly, Mark; Kaprio, Jaakko; Peltonen, Leena; Färkkilä, Markus; Wessman, Maija; Palotie, Aarno.
In: American Journal of Human Genetics, Vol. 82, No. 5, 2008, p. 1051-1063.Research output: Contribution to journal › Article › Scientific › peer-review
TY - JOUR
T1 - Consistently replicating locus linked to migraine on 10q22-q23
AU - Anttila, Verneri
AU - Nyholt, Dale R
AU - Kallela, Mikko
AU - Artto, Ville
AU - Vepsäläinen, Salli
AU - Jakkula, Eveliina
AU - Wennerström, Annika
AU - Tikka-Kleemola, Päivi
AU - Kaunisto, Mari A
AU - Hämäläinen, Eija
AU - Widen, Elisabeth
AU - Terwilliger, Joseph
AU - Merikangas, Kathleen
AU - Montgomery, Grant W
AU - Martin, Nicholas G
AU - Daly, Mark
AU - Kaprio, Jaakko
AU - Peltonen, Leena
AU - Färkkilä, Markus
AU - Wessman, Maija
AU - Palotie, Aarno
PY - 2008
Y1 - 2008
N2 - Here, we present the results of two genome-wide scans in two diverse populations in which a consistent use of recently introduced migraine-phenotyping methods detects and replicates a locus on 10q22-q23, with an additional independent replication. No genetic variants have been convincingly established in migraine, and although several loci have been reported, none of them has been consistently replicated. We employed the three known migraine-phenotyping methods (clinical end diagnosis, latent-class analysis, and trait-component analysis) with robust multiple testing correction in a large sample set of 1675 individuals from 210 migraine families from Finland and Australia. Genome-wide multipoint linkage analysis that used the Kong and Cox exponential model in Finns detected a locus on 10q22-q23 with highly significant evidence of linkage (LOD 7.68 at 103 cM in female-specific analysis). The Australian sample showed a LOD score of 3.50 at the same locus (100 cM), as did the independent Finnish replication study (LOD score 2.41, at 102 cM). In addition, four previously reported loci on 8q21, 14q21, 18q12, and Xp21 were also replicated. A shared-segment analysis of 10q22-q23 linked Finnish families identified a 1.6-9.5 cM segment, centered on 101 cM, which shows in-family homology in 95% of affected Finns. This region was further studied with 1323 SNPs. Although no significant association was observed, four regions warranting follow-up studies were identified. These results support the use of symptomology-based phenotyping in migraine and suggest that the 10q22-q23 locus probably contains one or more migraine susceptibility variants.
AB - Here, we present the results of two genome-wide scans in two diverse populations in which a consistent use of recently introduced migraine-phenotyping methods detects and replicates a locus on 10q22-q23, with an additional independent replication. No genetic variants have been convincingly established in migraine, and although several loci have been reported, none of them has been consistently replicated. We employed the three known migraine-phenotyping methods (clinical end diagnosis, latent-class analysis, and trait-component analysis) with robust multiple testing correction in a large sample set of 1675 individuals from 210 migraine families from Finland and Australia. Genome-wide multipoint linkage analysis that used the Kong and Cox exponential model in Finns detected a locus on 10q22-q23 with highly significant evidence of linkage (LOD 7.68 at 103 cM in female-specific analysis). The Australian sample showed a LOD score of 3.50 at the same locus (100 cM), as did the independent Finnish replication study (LOD score 2.41, at 102 cM). In addition, four previously reported loci on 8q21, 14q21, 18q12, and Xp21 were also replicated. A shared-segment analysis of 10q22-q23 linked Finnish families identified a 1.6-9.5 cM segment, centered on 101 cM, which shows in-family homology in 95% of affected Finns. This region was further studied with 1323 SNPs. Although no significant association was observed, four regions warranting follow-up studies were identified. These results support the use of symptomology-based phenotyping in migraine and suggest that the 10q22-q23 locus probably contains one or more migraine susceptibility variants.
KW - FAMILIAL HEMIPLEGIC MIGRAINE
KW - GENOME-WIDE ASSOCIATION
KW - LINKAGE ANALYSIS
KW - SUSCEPTIBILITY LOCUS
KW - COMPLEX TRAITS
KW - MACULAR DEGENERATION
KW - MULTIPLE-SCLEROSIS
KW - GENETIC DISSECTION
KW - PROSTATE-CANCER
KW - INFLUENCES RISK
U2 - 10.1016/j.ajhg.2008.03.003
DO - 10.1016/j.ajhg.2008.03.003
M3 - Article
VL - 82
SP - 1051
EP - 1063
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 5
ER -