TY - JOUR
T1 - Linkage disequilibrium patterns and tagSNP transferability among European populations
AU - Mueller, Jakob C.
AU - Lõhmussaar, Elin
AU - Mägi, Reedik
AU - Remm, Maido
AU - Bettecken, Thomas
AU - Lichtner, Peter
AU - Biskup, Saskia
AU - Illig, Thomas
AU - Pfeufer, Arne
AU - Luedemann, Jan
AU - Schreiber, Stefan
AU - Pramstaller, Peter
AU - Pichler, Irene
AU - Romeo, Giovanni
AU - Gaddi, Anthony
AU - Testa, Alessandra
AU - Wichmann, Heinz Erich
AU - Metspalu, Andres
AU - Meitinger, Thomas
N1 - Funding Information:
This work was supported by the National Genome Research Network and the Bioinformatics for the Functional Analysis of Mammalian Genomes project from the German Federal Ministry of Education and Research. A.M. and E.L. were partially supported by Targeted Funding EMRE 0182582s03, and E.L. had a fellowship from the E.U. grants Mol Tools 503155 and “Genera” to Estonian Biocentre. M.R. and R.M. were supported by a core grant from the Estonian Ministry of Education and Research. The recruitment of the south Tyrolian samples VIN and LAD was supported by a grant from the Autonomous Province Bolzano and from the Südtiroler Sparkasse, Bolzano. The project POPGEN is supported by the Deutsche Forschungsgemeinschaft research group FOR 423 (“Polygenic Disorders”). The SHIP studies are funded by the German Federal Ministry for Education and Research (grant 01ZZ96030), by the Ministry for Education, Research, and Cultural Affairs, and by the Ministry for Social Affairs of the State of Mecklenburg-West Pomerania. We gratefully acknowledge the participation of all probands, as well as the review of the manuscript by Jack Favor.
PY - 2005/3
Y1 - 2005/3
N2 - The pattern of linkage disequilibrium (LD) is critical for association studies, in which disease-causing variants are identified by allelic association with adjacent markers. The aim of this study is to compare the LD patterns in several distinct European populations. We analyzed four genomic regions (in total, 749 kb) containing candidate genes for complex traits. Individuals were genotyped for markers that are evenly distributed at an average spacing of -2-4 kb in eight population-based samples from ongoing epidemiological studies across Europe. The Centre d'Etude du Polymorphisme Humain (CEPH) trios of the HapMap project were included and were used as a reference population. In general, we observed a conservation of the LD patterns across European samples. Nevertheless, shifts in the positions of the boundaries of high-LD regions can be demonstrated between populations, when assessed by a novel procedure based on bootstrapping. Transferability of LD information among populations was also tested. In two of the analyzed gene regions, sets of tagging single-nucleotide polymorphisms (tagSNPs) selected from the HapMap CEPH trios performed surprisingly well in all local European samples. However, significant variation in the other two gene regions predicts a restricted applicability of CEPH-derived tagging markers. Simulations based on our data set show the extent to which further gain in tagSNP efficiency and transferability can be achieved by increased SNP density.
AB - The pattern of linkage disequilibrium (LD) is critical for association studies, in which disease-causing variants are identified by allelic association with adjacent markers. The aim of this study is to compare the LD patterns in several distinct European populations. We analyzed four genomic regions (in total, 749 kb) containing candidate genes for complex traits. Individuals were genotyped for markers that are evenly distributed at an average spacing of -2-4 kb in eight population-based samples from ongoing epidemiological studies across Europe. The Centre d'Etude du Polymorphisme Humain (CEPH) trios of the HapMap project were included and were used as a reference population. In general, we observed a conservation of the LD patterns across European samples. Nevertheless, shifts in the positions of the boundaries of high-LD regions can be demonstrated between populations, when assessed by a novel procedure based on bootstrapping. Transferability of LD information among populations was also tested. In two of the analyzed gene regions, sets of tagging single-nucleotide polymorphisms (tagSNPs) selected from the HapMap CEPH trios performed surprisingly well in all local European samples. However, significant variation in the other two gene regions predicts a restricted applicability of CEPH-derived tagging markers. Simulations based on our data set show the extent to which further gain in tagSNP efficiency and transferability can be achieved by increased SNP density.
UR - http://www.scopus.com/inward/record.url?scp=13844253254&partnerID=8YFLogxK
U2 - 10.1086/427925
DO - 10.1086/427925
M3 - Article
C2 - 15637659
AN - SCOPUS:13844253254
SN - 0002-9297
VL - 76
SP - 387
EP - 398
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 3
ER -