Evaluation of the SNP tagging approach in an independent population sample—array-based SNP discovery in Sami

Johansson, Åsa; Vavruch-Nilsson, Veronika; Cox, David; Frazer, Kelly A.; Gyllensten, Ulf

doi:10.1007/s00439-007-0379-2

Cited by 10 publications

(12 citation statements)

References 40 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A number of studies provide evidence that the extent of LD is much higher in the Saami as compared to that in other European populations. [20][21][22][23] This would provide an important power advantage, as higher LD leads to better genomic coverage. It has been proposed that association studies based on a map of modest marker density within a population isolate such as the Saami would provide a first rough identification of the region associated with a particular complex disease.…”

Section: Discussionmentioning

confidence: 99%

“…18,19 Several genetic studies have further suggested that the extent of linkage disequilibrium (LD) in the Saami is dramatically higher compared to that of outbred populations. [20][21][22][23] Higher levels of LD are observed in other population isolates as well. 24,25 Most of the genetic studies of genetically isolated populations were conducted involving young founder populations, in which the high extent of LD can be attributed to a founder effect.…”

Section: Introductionmentioning

confidence: 95%

See 1 more Smart Citation

A genome-wide association study for age-related hearing impairment in the Saami

et al. 2010

View full text Add to dashboard Cite

This study aimed at contributing to the elucidation of the genetic basis of age-related hearing impairment (ARHI), a common multifactorial disease with an important genetic contribution as demonstrated by heritability studies. We conducted a genomewide association study (GWAS) in the Finnish Saami, a small, ancient, genetically isolated population without evidence of demographic expansion. The choice of this study population was motivated by its anticipated higher extent of LD, potentially offering a substantial power advantage for association mapping. DNA samples and audiometric measurements were collected from 352 Finnish Saami individuals, aged between 50 and 75 years. To reduce the burden of multiple testing, we applied principal component (PC) analysis to the multivariate audiometric phenotype. The first three PCs captured 80% of the variation in hearing thresholds, while maintaining biologically important audiometric features. All subjects were genotyped with the Affymetrix 100 K chip. To account for multiple levels of relatedness among subjects, as well as for population stratification, association testing was performed using a mixed model. We summarised the top-ranking association signals for the three traits under study. The top-ranked SNP, rs457717 (P-value 3.55Â10 À7 ), was associated with PC3 and was localised in an intron of the IQ motif-containing GTPase-activating-like protein (IQGAP2). Intriguingly, the SNP rs161927 (P-value 0.000149), seventhranked for PC1, was positioned immediately downstream from the metabotropic glutamate receptor-7 gene (GRM7). As a previous GWAS of a European and Finnish sample set already suggested a role for GRM7 in ARHI, this study provides further evidence for the involvement of this gene.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

A genome-wide association study for age-related hearing impairment in the Saami

et al. 2010

View full text Add to dashboard Cite

show abstract

“…The transferability of HapMap-based selection of tSNPs using the reference CEU population to several other diverse populations of European ancestry has been demonstrated to be almost as effective for overall SNP coverage in selected genomic regions or randomly selected SNPs in the respective populations [46]–[50]. However, the coverage with tSNPs based on HapMap CEU data for a small subset of specific genes or SNPs may be lower in certain populations despite overall similar coverage [51], particularly for isolated indigenous populations [52]. Other than the data provided by the HapMap project, we are not aware of complete sequence variant information available for validation of the transferability of tSNP panels that were designed based on HapMap data to other study populations.…”

Section: Discussionmentioning

confidence: 99%

Assembly of Inflammation-Related Genes for Pathway-Focused Genetic Analysis

Loza

McCall

et al. 2007

PLoS ONE

View full text Add to dashboard Cite

Recent identifications of associations between novel variants in inflammation-related genes and several common diseases emphasize the need for systematic evaluations of these genes in disease susceptibility. Considering that many genes are involved in the complex inflammation responses and many genetic variants in these genes have the potential to alter the functions and expression of these genes, we assembled a list of key inflammation-related genes to facilitate the identification of genetic associations of diseases with an inflammation-related etiology. We first reviewed various phases of inflammation responses, including the development of immune cells, sensing of danger, influx of cells to sites of insult, activation and functional responses of immune and non-immune cells, and resolution of the immune response. Assisted by the Ingenuity Pathway Analysis, we then identified 17 functional sub-pathways that are involved in one or multiple phases. This organization would greatly increase the chance of detecting gene-gene interactions by hierarchical clustering of genes with their functional closeness in a pathway. Finally, as an example application, we have developed tagging single nucleotide polymorphism (tSNP) arrays for populations of European and African descent to capture all the common variants of these key inflammation-related genes. Assays of these tSNPs have been designed and assembled into two Affymetrix ParAllele customized chips, one each for European (12,011 SNPs) and African (21,542 SNPs) populations. These tSNPs have greater coverage for these inflammation-related genes compared to the existing genome-wide arrays, particularly in the African population. These tSNP arrays can facilitate systematic evaluation of inflammation pathways in disease susceptibility. For additional applications, other genotyping platforms could also be employed. For existing genome-wide association data, this list of key inflammation-related genes and associated subpathways can facilitate comprehensive inflammation pathway- focused association analyses.

show abstract

“…These results indicate that the potential for 'drift mapping' , anticipated based on simulations and limited empirical data, has been greatly overestimated. 2,9,10,13,[15][16][17] Most of the cited empirical work on the extent of LD in the Saami was based on microsatellite markers. 2,10,15,16 These studies only report P-values from pairwise significance tests of LD.…”

Section: Discussionmentioning

confidence: 99%

“…12,14 Due to their demographic history, it has been suggested that the Saami offer great potential for 'drift mapping' , and hence, more economic GWASs. 2,10,13,[15][16][17] However, this has been substantiated with only very limited empirical data, most of which predate the HapMap project.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide SNP analysis reveals no gain in power for association studies of common variants in the Finnish Saami

et al. 2009

View full text Add to dashboard Cite

The Saami from Fennoscandia are believed to represent an ancient, genetically isolated population with no evidence of population expansion. Theoretical work has indicated that under this demographic scenario, extensive linkage disequilibrium (LD) is generated by genetic drift. Therefore, it has been suggested that the Saami would be particularly suited for genetic association studies, offering a substantial power advantage and allowing more economic study designs. However, no study has yet assessed this claim. As part of a GWAS for a complex trait, we evaluated the relative power for association studies of common variants in the Finnish Saami. LD patterns in the Saami were very similar to those in the non-African HapMap reference panels. Haplotype diversity was reduced and, on average, levels of LD were higher in the Saami as compared with those in the HapMap panels. However, using a 'hidden' SNP approach we show that this does not translate into a power gain in association studies. Contrary to earlier claims, we show that for a given set of common SNPs, genomic coverage attained in the Saami is similar to that in the non-African HapMap panels. Nevertheless, the reduced haplotype diversity could potentially facilitate gene identification, especially if multiple rare variants play a role in disease etiology. Our results further indicate that the HapMap is a useful resource for genetic studies in the Saami.

show abstract

Evaluation of the SNP tagging approach in an independent population sample—array-based SNP discovery in Sami

Cited by 10 publications

References 40 publications

A genome-wide association study for age-related hearing impairment in the Saami

A genome-wide association study for age-related hearing impairment in the Saami

Assembly of Inflammation-Related Genes for Pathway-Focused Genetic Analysis

Genome-wide SNP analysis reveals no gain in power for association studies of common variants in the Finnish Saami

Contact Info

Product

Resources

About