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Statistical methods for assessing linkage disequilibrium at the HLA‐A, B, C loci
Author(s) -
KARLIN S.,
PIAZZA A.
Publication year - 1981
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/j.1469-1809.1981.tb00308.x
Subject(s) - linkage disequilibrium , disequilibrium , locus (genetics) , genetics , pairwise comparison , biology , population , population genetics , haplotype , allele , statistics , mathematics , gene , demography , medicine , sociology , ophthalmology
SUMMARY A number of standard and new statistics for measuring linkage disequilibrium are introduced applicable to any multilocus system. Included are the usual pairwise gametic disequilibrium function, D, the Lewontin disequilibrium index, D L , a Euclidean disequilibrium distance, D E , a hierarchy of stratified linkage disequilibrium functions (e.g. a pairwise disequilibrium value conditioned on the value of a third locus) and an averaged conditional disequilibrium expression, D W . Various global second order measures of disequilibrium are proposed partly based on contingency table statistics and weighted pairwise disequilibrium quantities. A non‐parametric (stochastic) comparison assessment for global linkage disequilibrium is also developed. These measures are compared and contrasted at the HLA‐A, B, C gene complex for a sample of 2000 haplotypes from a healthy Austrian population. Several results from applying these methods include: (1) Of the various pairwise disequilibrium measures examined, D, D E and D W correlated very closely with each other but differ from D L . (2) The ‘third‐order interaction’ between two loci conditional on an allele (or group of alleles) at a third locus indicated that HLA‐AB maintains the classical disequilibrium pairings only for conditioning on C X (the blank allele at locus C), and they mostly disappear for conditioning on C 1 to C 5 . (3) Subpopulations involving C 3 or C 4 alleles exhibit the significant new combinations A 33 B 17 and A 2 B 15 . (4) The B, C loci have a higher total linkage disequilibrium than A, B and A, C; more than expected by mapping distance relationships. (5) The total linkage disequilibrium was significantly larger for conditioning on C X compared to C X (non‐C X ), but smaller for the population conditioned by {C 3 , C 4 }. A number of interpretations of the results with respect to heterogeneity classifications of populations are discussed.