Single-Nucleotide Polymorphism Alleles in the Insulin Receptor Gene Are Associated with Typical Migraine

McCarthy, Linda; Hosford, David A.; Riley, John; Bird, Michael I.; White, Nicola J.; Hewett, Duncan R.; Peroutka, Stephen J.; Griffiths, Lyn R.; Boyd, Peter R.; Lea, Rodney Arthur; Bhatti, Shahid M.; Hosking, Louise K.; Hood, Chris M.; Jones, Keith; Handley, Abigail R.; Rallan, Raj; Lewis, Karen; Yeo, Astrid; Williams, Pauline; Priest, Richard; Khan, Parveen; Donnelly, Christine; Lumsden, S; O’Sullivan, Jennifer; See, Chee Gee; Smart, Devi H.; Shaw‐Hawkins, Sue; Patel, Jaymini; Langrish, Tony C.; Feniuk, W.; Knowles, Richard G.; Thomas, Michelle; Libri, Vincenzo; Montgomery, Douglas S.; Manasco, Penny K.; Xu, Chun‐Fang; Dykes, Colin W.; Humphrey, P. P. A.; Roses, Allen D.; Purvis, Ian J.

doi:10.1006/geno.2001.6647

Cited by 122 publications

(27 citation statements)

References 43 publications

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“…The 795 individuals are controls for a migraine study of the insulin receptor (INSR) region (10). Markers have been entered in the dbSNP database (http:͞͞www.ncbi.nlm.nih.gov͞SNP͞), which creates nine-character accession numbers that are far too long for human communication.…”

Section: Chromosome 19mentioning

confidence: 99%

The first linkage disequilibrium (LD) maps: Delineation of hot and cold blocks by diplotype analysis

Maniatis

Collins

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

170

166

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Linkage disequilibrium (LD) provides information about positional cloning, linkage, and evolution that cannot be inferred from other evidence, even when a correct sequence and a linkage map based on more than a handful of families become available. We present theory to construct an LD map for which distances are additive and population-specific maps are expected to be approximately proportional. For this purpose, there is only a modest difference in relative efficiency of haplotypes and diplotypes: resolving the latter into 2-locus haplotypes has significant cost or error and increases information by about 50%. LD maps for a cold spot in 19p13.3 and a more typical region in 3q21 are optimized by interval estimates. For a random sample and trustworthy map the value of LD at large distance can be predicted reliably from information over a small distance and does not depend on the evolutionary variance unless the sample size approaches the population size. Values of the association probability that can be distinguished from the value at large distance are determined not by population size but by time since a critical bottleneck. In these examples, omission of markers with significant HardyWeinberg disequilibrium does not improve the map, and widely discrepant draft sequences have similar estimates of the genetic parameters. The LD cold spot in 19p13.3 gives an unusually high estimate of time, supporting an argument that this relationship is general. As predicted for a region with ancient haplotypes or uniformly high recombination, there is no clear evidence of LD clustering. On the contrary, the 3q21 region is resolved into alternating blocks of stable and decreasing LD, as expected from crossover clustering. Construction of a genomewide LD map requires data not yet available, which may be complemented but not replaced by a catalog of haplotypes. P ositional cloning of genes for disease susceptibility depends on linkage and ''allelic association'' (also called ''linkage disequilibrium'' or LD). A cold spot for LD is an interval in which LD declines rapidly with distance: neither linkage nor LD is proportional to the sequence-based map. To the extent that LD mirrors recombination it can extend the low resolution of linkage: a cold spot for LD is a hot spot for recombination and vice versa. However, this correspondence is disturbed by other factors that cannot be reliably predicted. To the extent that these phenomena are important, both the physical and linkage maps are unreliable guides to LD. We need an LD map to facilitate positional cloning, extend the resolution of the linkage map, compare populations, infer their paleodemography, and detect selective sweeps and other events of evolutionary interest. LD mapping is at the stage of linkage maps nearly a century ago, with the same promise.The definitive property of a chromosome map, whether physical or genetic, is that its distances are additive. With this constraint, we require a standard LD map to which populationspecific maps are approximately proportional. Here...

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Section: Chromosome 19mentioning

confidence: 99%

The first linkage disequilibrium (LD) maps: Delineation of hot and cold blocks by diplotype analysis

Maniatis

Collins

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

170

166

View full text Add to dashboard Cite

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“…7 Recently identified SNPs in the insulin receptor gene were associated with migraine by LD mapping. 8 LD therefore plays an important role in mapping complex disease genes 6 and in proposed genome-wide scans. 9 With the release of the first draft sequence of the entire human genome, and the concomitant output from The SNP Consortium 10 culminating in the release of 2 400 000 SNPs (October 2001), it has become possible to rapidly identify and map genetic variation to specific fully sequenced chromosomal regions.…”

Section: Introductionmentioning

confidence: 99%

Linkage disequilibrium mapping identifies a 390 kb region associated with CYP2D6 poor drug metabolising activity

Hosking

Boyd

et al. 2002

Pharmacogenomics J

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The cytochrome p450 enzyme, CYP2D6, metabolises approximately 20% of marketed drugs. CYP2D6 multiple variants are associated with altered enzyme activities. Genotyping 1018 Caucasians for CYP2D6 polymorphisms (G1846A, delT1707, delA2549 and A2935C), known to result in the recessive CYP2D6 poor drug metaboliser (PM) phenotype, identified 41 individuals with predicted PM phenotype. These 41 individuals were classified as 'cases'. Single nucleotide polymorphisms (SNPs) mapping within an 880 kb region flanking CYP2D6, were identified to evaluate potential association between genetic variation and the CYP2D6 PM phenotype. The 41 PM cases and 977 controls were genotyped and analysed for 27 SNPs. Associations were observed across a 390 kb region between 14 SNPs and the PM phenotype (P values from 6.20 ϫ 10 Ϫ4 to 4.54 ϫ 10 Ϫ35 ). Haplotype analysis revealed more significant levels of association (P ϭ 3.54 ϫ 10 Ϫ56 ). Strong (DЈ Ͼ 0.7) linkage disequilibrium (LD) between SNPs was observed across the same 390 kb region associated with the CYP2D6 phenotype. The observed phenotype:genotype association reached genome-wide levels of significance, and supports the strategy for potential application of LD mapping and whole genome association scans to pharmacogenetic studies.

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“…Alternatively, specific genetic polymorphisms play important roles for certain aspects of recurrent headache, such as onset and prognosis. A polymorphism of the insulin receptor gene located on chromosome 19 has recently been proposed as one susceptibility gene for non-familial migraine (McCarthy et al, 2001). …”

Section: Discussionmentioning

confidence: 99%

Genetic and Environmental Influences on Expression of Recurrent Headache as a Function of the Reporting Age in Twins

Svensson

Larsson²,

Waldenlind³

et al. 2002

Twin Research

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Single-Nucleotide Polymorphism Alleles in the Insulin Receptor Gene Are Associated with Typical Migraine

Cited by 122 publications

References 43 publications

The first linkage disequilibrium (LD) maps: Delineation of hot and cold blocks by diplotype analysis

The first linkage disequilibrium (LD) maps: Delineation of hot and cold blocks by diplotype analysis

Linkage disequilibrium mapping identifies a 390 kb region associated with CYP2D6 poor drug metabolising activity

Genetic and Environmental Influences on Expression of Recurrent Headache as a Function of the Reporting Age in Twins

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