A Susceptibility Locus for Migraine with Aura, on Chromosome 4q24

Wessman, Maija; Kallela, Mikko; Kaunisto, Mari A.; Marttila, Pia; Sobel, Eric M.; Hartiala, Jaana; Oswell, Greg; Leal, Suzanne M.; Papp, Jeanette C.; Hämäläinen, Eija; Broas, Petra; Joslyn, Geoffrey; Hovatta, Iiris; Hiekkalinna, Tero; Kaprio, Jaakko; Ott, Jürg; Cantor, Rita M.; Zwart, John‐Anker; Ilmavirta, Matti; Havanka, Hannele; Färkkilä, Markus; Peltonen, Leena; Palotie, Aarno

doi:10.1086/339078

Cited by 144 publications

(120 citation statements)

References 67 publications

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“…Each proband in the GeneQuest family must have another affected sib to be included in the study. The necessity of a restrictive phenotype has been noted as a key determinant in identifying significant genetic loci for complex traits and confirming genetic, rather than environmental contributions (Van Eerdewegh et al 2002;Wessman et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Four SNPS on Chromosome 9p21 Confer Risk to Premature, Familial CAD and MI in an American Caucasian Population (GeneQuest)

Abdullah

Shen

et al. 2008

Annals of Human Genetics

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SummaryGenome-wide association studies have separately identified four single nucleotide polymorphisms (SNPs) on chromosome 9p21 that confer susceptibility to coronary artery disease (CAD) and myocardial infarction (MI). This study presents the first analysis of these SNPs (rs10757274, rs2383206, rs2383207, and rs10757278) in a premature, familial CAD/MI population (GeneQuest). We performed a case-control analysis of the GeneQuest Caucasian population with 310 cases with premature CAD and MI (average age at onset of 40.3 ± 5.1) and 560 non-CAD controls to determine if these SNPs are associated with risk of CAD using both the population-based and family-based association study designs. The four SNPs are significantly associated with premature and familial MI and CAD in the GeneQuest Caucasian population (allelic P = 6.61 × 10 −7 to 1.87 × 10 −8 ). Sib-TDT analysis showed that three of the four SNPs could confer significant susceptibility to premature CAD and MI. These results indicate that the four SNPs on chromosome 9p21 are also associated with premature, familial CAD.

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Section: Discussionmentioning

confidence: 99%

Four SNPS on Chromosome 9p21 Confer Risk to Premature, Familial CAD and MI in an American Caucasian Population (GeneQuest)

Abdullah

Shen

et al. 2008

Annals of Human Genetics

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“…The ascertained pedigree structures being used in ongoing studies of migraine 24,25 and schizophrenia 26 in Finland were used for simulation analyses. The migraine sample included multigenerational pedigrees, whereas the schizophrenia sample consisted of mostly nuclear pedigrees.…”

Section: Methods To Be Comparedmentioning

confidence: 99%

“…23 Different software applying the same or similar tests may have different properties due to differences in implementation. We compared performance using simulated data based on datasets ascertained for studies of migraine 24,25 and schizophrenia 26 in Finland, on which joint association and linkage studies are ongoing. In addition, we used our phenogenetic evolutionary simulator, ForSim, 27 to simulate data under an oligogenic model with environmental and genetic factors contributing to disease in a population.…”

Section: Introductionmentioning

confidence: 99%

On the statistical properties of family-based association tests in datasets containing both pedigrees and unrelated case–control samples

et al. 2011

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A common approach to genetic mapping of loci for complex diseases is to perform a genome-wide association study (GWAS) by analyzing a vast number of SNP markers in cohorts of unrelated cases and controls. A direct motivation for the case-control design is that unrelated, affected individuals can be easier to collect than large families with multiple affected persons in the Western world. Despite its higher potential power, investigators have not actively pursued family ascertainment in part because of a dearth of methods for analyzing such correlated data on a large scale. We examine the statistical properties of several commonly used family-based association tests, as to their performance using real-life mixtures of families and singletons taken from our own migraine and schizophrenia studies, as well as population-based data for a complex trait simulated with the evolutionary phenogenetic simulator, ForSim. In virtually every situation, the full likelihood-based methods in the PSEUDOMARKER program outperformed those implemented in FBAT, GENEHUNTER TDT, PLINK (family-based options), HRR/HHRR, QTDT, TRANSMIT, UNPHASED, MENDEL, and LAMP. We further show that GWAS is much more powerful when family samples are used rather than unrelateds, on a genotype-by-genotype basis.

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“…Strong associations were found between migraine and group-specific component GC 1F-1F and esterase-D ESD 2-2, located on chromosomes 4 and 13, respectively. Wessman et al [73] performed a genome-wide screen of 50 multigenerational Finnish families with MA, using 350 polymorphic microsatellite markers with an average intermarker distance of 11 cM. They found significant linkage with D4S1647 on 4q24 and no other chromosomal region.…”

Section: Genetics Of the Typical Migraines: Genome-wide Scansmentioning

confidence: 99%

The “typical” migraines: genetic studies and some practical considerations

2003

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"Typical" migraine as a complex disease: genetic epidemiology, twin and segregation analysis studies That migraine runs in families is an ancient observation. Familiarity however is not synonymous with heritability, especially given the wide prevalence of migraine and the possibility that familial occurrence is due to chance. In order to assess the heritability of migraine, e.g. the rate of variance attributable to genetic factors, the disease risk of relatives of migraine probands is determined and compared to that found in the general population. Several surveys indicated that first-and sometimes also seconddegree relatives of migraine probands show increased risk for migraine: a two-fold increased risk for migraine without aura (MO) and 1.4 for migraine with aura (MA) in the case of first-degree relatives of MO probands, and a 4-fold risk for MA in the case of first-degree relatives of MA probands [1]. An increased disease risk does not however prove heritability, since it may result from shared environmental factors. It is therefore interesting to note that at least one genetic epidemiology survey found an increased disease risk for migraine in first-degree relatives compared to spouses of migraine probands, who presumably share environmental factors at least for some time in their lives. Notably however, the relative risk for spouses was increased compared to the general population, which implies some degree of assorted mating or shared environmental influences [1]. Studies of heritability performed according to disease risk comparisons came to high rates of genetic determination, e.g. 60%-80% for MO and MA [2].Better ways of analysing heritability of migraine are studies of monozygotic versus dizygotic twins, especially when reared-together and reared-apart (adopted) identical twins are considered. Several twin studies have been performed in migraine Pasquale Montagna Pietro Cortelli Mirella MochiAbstract Epidemiological genetic, family and twin studies show that the typical migraines carry a substantial genetic risk; they are currently conceptualized as complex genetic diseases. Several genetic association and linkage studies have been performed in the typical migraines. Candidate gene studies based on "a priori" pathogenic models of migraine (migraine as a calcium channelopathy; a mitochondrial DNA disorder; a disorder in the metabolism of serotonin or dopamine; in vascular risk factors or in the inflammation cascade; etc.) did not result in uniformely accepted findings. Linkage and genome wide scans gave evidence for several genetic susceptibility loci, still however in need of confirmation. Careful dissection of the clinical phenotypes and trigger factors shall greatly help future efforts in the quest for the genetic basis of the typical migraines.

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A Susceptibility Locus for Migraine with Aura, on Chromosome 4q24

Cited by 144 publications

References 67 publications

Four SNPS on Chromosome 9p21 Confer Risk to Premature, Familial CAD and MI in an American Caucasian Population (GeneQuest)

Four SNPS on Chromosome 9p21 Confer Risk to Premature, Familial CAD and MI in an American Caucasian Population (GeneQuest)

On the statistical properties of family-based association tests in datasets containing both pedigrees and unrelated case–control samples

The “typical” migraines: genetic studies and some practical considerations

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