title: 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)=0.004 across 25 SNPs, range 0.001-0.008) and it was not significantly higher for pathogen response SNPs (F(st)=0.004) than for other SNPs (F(st)=0.003, P=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 -0.10) 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.
authors.affiliation: Institute for Biopharmaceutical Sciences, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.
authors.forename: Ciara
authors.initials: C
authors.lastname: Dolan
authors.forename: Aisling
authors.initials: A
authors.lastname: O'Halloran
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Bradley
authors.forename: David T
authors.initials: DT
authors.lastname: Croke
authors.forename: Alun
authors.initials: A
authors.lastname: Evans
authors.forename: John K
authors.initials: JK
authors.lastname: O'Brien
authors.forename: Patrick
authors.initials: P
authors.lastname: Dicker
authors.forename: Denis C
authors.initials: DC
authors.lastname: Shields
mesh_terms: D015239:Arylsulfotransferase / Q000235:genetics; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005828:Genetics, Population; D015234:HLA-A Antigens / Q000235:genetics; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D013217:Starvation; D014376:Tuberculosis / Q000235:genetics* / Q000401:mortality*; D044465:White People / Q000235:genetics
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D015234:HLA-A Antigens; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human