Linkage disequilibrium and demographic history of the isolated population of the Faroe Islands

Abstract

The isolated population of the Faroe Islands has a history of recent expansion after being limited to a small size for centuries. Such an isolated population may be ideal for linkage disequilibrium mapping of disease genes if linkage disequilibrium (LD) extends over large regions. Analyses of 18 markers on 12q24.3, spanning a region of 4.3 Mb (16 cM), revealed extensive LD in the Faroese population. Maximum LD was found between marker pairs separated by more than 3.8 Mb. The same region had a maximum LD of only 1.2 and 1.4 Mb respectively in two outbred Danish and British populations analysed here for comparison. The analyses of gene diversity excess at 15 unlinked microsatellite markers did not reveal any sign of a severe bottleneck to have occurred within approximately 1200 years' history of the Faroese population. The extensive LD in this population may, therefore, have arisen primarily by random genetic drift. The implications for future gene mapping studies are discussed.

A genome-wide search for alleles and haplotypes associated with autism and related pervasive developmental disorders on the Faroe Islands

“…63,65 Conflicting evidence has, however, been reported regarding the actual degree of homogeneity of isolated populations. 64 A previous study on the Faroese population 25 indicated extensive LD among the 15 markers surveyed. Furthermore, the allelic diversity was smaller, although nonsignificant in the Faroese population compared to outbred populations.…”

“…Despite lack of evidence for a strong population bottleneck on the Faroe Islands, the population is considered suitable for LD mapping of complex diseases. 25 To avoid bias due to population stratification, it is essential that cases and controls are subsamples of the same panmictic population and share a similar genetic history. Based on Wright's F ST and modelbased clustering analyses, this essential assumption seems valid for our sample of cases and controls.…”

“…No correction for type I error was made, despite the large number of tests performed, but a relatively low level of significance (Pp0.01) was chosen. Since many of the markers are in close proximity and in extensive LD, 25 the association tests performed cannot be considered independent, and the standard procedure for correction for type I error will therefore be too conservative. There is no generally accepted method to make the appropriate correction, although simulation-based statistics are being explored.…”

“…Furthermore, this recent founding, isolation, and relatively rapid expansion of the Faroese population is reflected in the extensive background linkage disequilibrium (LD) observed in the population. 25 In the present study, distantly related individuals with childhood autism and related pervasive developmental disorders (PDDs) from the Faroe Islands were genotyped for polymorphic markers distributed throughout the human genome in the search for allele and haplotype association. Association between specific markers and the disorder suggests that the markers are in LD with, and therefore presumably lie close to a susceptibility gene, and may thus contribute to the localization of candidate regions for autism.…”

A genome-wide study of panic disorder suggests the amiloride-sensitive cation channel 1 as a candidate gene

“…The Bonferroni correction, which assumes independence between the individual tests, was considered too conservative. As many of the markers are in close proximity, they are likely in LD, 41 and the association tests performed are hence not independent. However, to compensate for multiple testing and reduce the type I error rate, we applied relatively low thresholds in stage 1 and 2.…”