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Patterns of linkage disequilibrium and haplotype distribution in disease candidate genes

Ji-Rong Long1, Lan-Juan Zhao12, Peng-Yuan Liu1, Yan Lu1, Volodymyr Dvornyk1, Hui Shen12, Yong-Jun Liu12, Yuan-Yuan Zhang1, Dong-Hai Xiong12, Peng Xiao12 and Hong-Wen Deng123*

Author Affiliations

1 Osteoporosis Research Center, Creighton University, Omaha, NE 68131, USA

2 Department of Biomedical Sciences, Creighton University, Omaha, NE 68131, USA

3 Laboratory of Molecular and Statistical Genetics, College of Life Sciences Hunan Normal University, Changsha, Hunan 410081, P. R. China

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BMC Genetics 2004, 5:11  doi:10.1186/1471-2156-5-11

Published: 24 May 2004



The adequacy of association studies for complex diseases depends critically on the existence of linkage disequilibrium (LD) between functional alleles and surrounding SNP markers.


We examined the patterns of LD and haplotype distribution in eight candidate genes for osteoporosis and/or obesity using 31 SNPs in 1,873 subjects. These eight genes are apolipoprotein E (APOE), type I collagen α1 (COL1A1), estrogen receptor-α (ER-α), leptin receptor (LEPR), parathyroid hormone (PTH)/PTH-related peptide receptor type 1 (PTHR1), transforming growth factor-β1 (TGF-β1), uncoupling protein 3 (UCP3), and vitamin D (1,25-dihydroxyvitamin D3) receptor (VDR). Yin yang haplotypes, two high-frequency haplotypes composed of completely mismatching SNP alleles, were examined. To quantify LD patterns, two common measures of LD, D' and r2, were calculated for the SNPs within the genes. The haplotype distribution varied in the different genes. Yin yang haplotypes were observed only in PTHR1 and UCP3. D' ranged from 0.020 to 1.000 with the average of 0.475, whereas the average r2 was 0.158 (ranging from 0.000 to 0.883). A decay of LD was observed as the intermarker distance increased, however, there was a great difference in LD characteristics of different genes or even in different regions within gene.


The differences in haplotype distributions and LD patterns among the genes underscore the importance of characterizing genomic regions of interest prior to association studies.

linkage disequilibrium (LD); haplotype; single nucleotide polymorphism (SNP)