Evaluating differences in linkage disequilibrium between populations.
We propose two methods to evaluate the statistical significance of differences in linkage disequilibrium (LD) between populations, where LD is measured by the standardised parameter D'. The first method is based on bootstrapping individuals within populations in order to test LD differences for each pair of loci. Using this approach we propose a solution to the problem of testing multiple locus-pairs by means of a single test for the number of pairs that exhibit significant LD differences among populations. The second method provides the Bayesian posterior probability that one population has greater LD than the other for each locus pair. Both methods can handle genotypes with unknown phase, and are demonstrated using two data sets. For the purpose of demonstration, we apply the methods to two different sets of data from humans. First, we explore the issue of LD differences between reproductively isolated populations using a new data set of twelve Xq25 microsatellites, typed in four European populations. Second, we examine evidence for LD differences between Alzheimer cases and controls from the Icelandic population using 19 single nucleotide polymorphisms (SNPs) from a 97 kb region flanking the Apolipoprotein E (APOE) gene on chromosome 19.
deCODE genetics, 101 Reykjavik, Iceland. birgirhr@hi.is
Birgir
B
Hrafnkelsson
Agnar
A
Helgason
Gudbjorn F
GF
Jonsson
Daniel F
DF
Gudbjartsson
Thorlakur
T
Jonsson
Sverrir
S
Thorvaldsson
Hreinn
H
Stefansson
Valgerdur
V
Steinthorsdottir
Nanna
N
Vidarsdottir
Derek
D
Middleton
Henning S
HS
Petersen
Conrado
C
Martinez
Jon
J
Snaedal
Palmi V
PV
Jonsson
Sigurbjorn
S
Bjornsson
Jeffrey R
JR
Gulcher
Kari
K
Stefansson
D000544:Alzheimer Disease / Q000235:genetics; D041321:Chromosomes, Human, X; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006801:Humans; D007055:Iceland; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics