1. Identification of QTL genes for BMD variation using both linkage and gene-based association approaches.
- Author
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Li GH, Cheung CL, Xiao SM, Lau KS, Gao Y, Bow CH, Huang QY, Sham PC, and Kung AW
- Subjects
- Adult, Asian People, Case-Control Studies, Chromosome Mapping, Female, Genetic Variation, Genotype, Humans, Lod Score, Male, Meta-Analysis as Topic, Middle Aged, Pedigree, White People, Bone Density genetics, Chromosomes, Human, Pair 15 genetics, Femur Neck physiopathology, Genetic Linkage, Osteoporosis genetics, Quantitative Trait Loci
- Abstract
Low bone mineral density (BMD) is a risk factor for osteoporotic fracture with a high heritability. Previous large scale linkage study in Northern Chinese has identified four significant quantitative trait loci (QTL) for BMD variation on chromosome 2q24, 5q21, 7p21 and 13q21. We performed a replication study of these four QTL in 1,459 Southern Chinese from 306 pedigrees. Successful replication was observed on chromosome 5q21 for femoral neck BMD with a LOD score of 1.38 (nominal p value = 0.006). We have previously identified this locus in a genome scan meta-analysis of BMD variation in a white population. Subsequent QTL-wide gene-based association analysis in 800 subjects with extreme BMD identified CAST and ERAP1 as novel BMD candidate genes (empirical p value of 0.032 and 0.014, respectively). The associations were independently replicated in a Northern European population (empirical p value of 0.01 and 0.004 for CAST and ERAP1, respectively). These findings provide further evidence that 5q21 is a BMD QTL, and CAST and ERAP1 may be associated with femoral neck BMD variation.
- Published
- 2011
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