Genetic stratification of pathogen-response-related and other variants within a homogeneous Caucasian Irish population

Abstract

Selection pressures from pathogens impact on the worldwide geographic distribution of polymorphisms in certain pathogen-response-associated genes. Such gene-specific effects could lead to confounding by geographic disease associations. We wished to determine if such constraints impinge on the genetic structure of a population of Irish patients and whether variants associated with responses to pathogens showed greater stratification. The counties of origin of each subject's grandparents were used as the geographic variable. F st, proportional to the extent of population structure, was low (mean F st ¼ 0.004 across 25 SNPs, range 0.001 -0.008) and it was not significantly higher for pathogen response SNPs (F st ¼ 0.004) than for other SNPs (F st ¼ 0.003, P ¼ 0.21). Correspondence analysis revealed weak trends primarily in approximately northeast to southwest and secondarily in northwest to southeast directions. One-dimensional spatial autocorrelation analysis revealed a weak (Moran's I autocorrelation of À0.10) tendency for SNP frequencies to diverge with greater distance. Two-dimensional autocorrelation indicated a northeast to southwest gradient that was similar for both the pathogen response and other SNPs. The southeastern county, Wexford, showed a distinctive pattern, perhaps consistent with Anglo-Norman settlements. In conclusion, these results indicate that pathogen response SNPs do not exhibit significantly more population structure than other SNPs within this Caucasian population. This suggests that the specific population structure of particular genes may not typically be a cause of strong confounding in genetic studies where population structure is controlled.

An assessment of the Irish population for large-scale genetic mapping studies involving epilepsy and other complex diseases

“…It is also probable that some degree of genetic structure between Britain and Ireland will be resolved as more ancestral informative markers are identified as has been the case within British populations. 23,24 Contrary to studies of the Y chromosome, and in agreement with a previous report 25 our assessment failed to detect evidence of population structure within Ireland even when only individuals with four grandparents from the same province were considered. 10,25,26 It is reasonable to assume that by considering a larger number of SNPs (such as those currently available on WGA platforms) this picture would change as Irish specific ancestry informative SNPs begin to emerge.…”

Geographical, urban/rural and socioeconomic variations in nonmelanoma skin cancer incidence: a population-based study in Ireland

“…Similar comments apply to genetic variation. There is some evidence to suggest there are genetic differences within Ireland, 23–25 but given that the native population appears relatively homogenous ancestrally, 9 and that the NMSC susceptibility genes so far identified confer only very modest increased risks, 26,27 it does not seem likely that genetic variation can explain the geographical patterns observed.…”

The Impact on Coronary Artery Disease of Common Polymorphisms Known to Modulate Responses to Pathogens

“…This comprised 386 individuals who were employees of an Irish financial institution (Table 1). Previous analysis of the ACS population indicated evidence for only very mild geographic stratification of genetic background in Ireland (Dolan et al 2005).…”