caa a22 4500 445860936 CHVBK 20180317145442.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s00439-011-0972-2 doi (NATIONALLICENCE)springer-10.1007/s00439-011-0972-2 Identification of QTL genes for BMD variation using both linkage and gene-based association approaches [Elektronische Daten] [Gloria Li, Ching-Lung Cheung, Su-Mei Xiao, Kam-Shing Lau, Yi Gao, Cora Bow, Qing-Yang Huang, Pak-Chung Sham, Annie Kung] 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. The Author(s), 2011 Li Gloria Department of Medicine, The University of Hong Kong, Lab Block, 21 Sassoon Road, Hong Kong, Hong Kong aut Cheung Ching-Lung Department of Medicine, The University of Hong Kong, Lab Block, 21 Sassoon Road, Hong Kong, Hong Kong aut Xiao Su-Mei Department of Medicine, The University of Hong Kong, Lab Block, 21 Sassoon Road, Hong Kong, Hong Kong aut Lau Kam-Shing Department of Medicine, The University of Hong Kong, Lab Block, 21 Sassoon Road, Hong Kong, Hong Kong aut Gao Yi Department of Medicine, The University of Hong Kong, Lab Block, 21 Sassoon Road, Hong Kong, Hong Kong aut Bow Cora Department of Medicine, The University of Hong Kong, Lab Block, 21 Sassoon Road, Hong Kong, Hong Kong aut Huang Qing-Yang Department of Medicine, The University of Hong Kong, Lab Block, 21 Sassoon Road, Hong Kong, Hong Kong aut Sham Pak-Chung Department of Psychiatry, The University of Hong Kong, Hong Kong, Hong Kong aut Kung Annie Department of Medicine, The University of Hong Kong, Lab Block, 21 Sassoon Road, Hong Kong, Hong Kong aut Human Genetics Springer-Verlag 130/4(2011-10-01), 539-546 0340-6717 130:4<539 2011 130 439 https://doi.org/10.1007/s00439-011-0972-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-011-0972-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Li Gloria Department of Medicine, The University of Hong Kong, Lab Block, 21 Sassoon Road, Hong Kong, Hong Kong aut NATIONALLICENCE 700 1- Cheung Ching-Lung Department of Medicine, The University of Hong Kong, Lab Block, 21 Sassoon Road, Hong Kong, Hong Kong aut NATIONALLICENCE 700 1- Xiao Su-Mei Department of Medicine, The University of Hong Kong, Lab Block, 21 Sassoon Road, Hong Kong, Hong Kong aut NATIONALLICENCE 700 1- Lau Kam-Shing Department of Medicine, The University of Hong Kong, Lab Block, 21 Sassoon Road, Hong Kong, Hong Kong aut NATIONALLICENCE 700 1- Gao Yi Department of Medicine, The University of Hong Kong, Lab Block, 21 Sassoon Road, Hong Kong, Hong Kong aut NATIONALLICENCE 700 1- Bow Cora Department of Medicine, The University of Hong Kong, Lab Block, 21 Sassoon Road, Hong Kong, Hong Kong aut NATIONALLICENCE 700 1- Huang Qing-Yang Department of Medicine, The University of Hong Kong, Lab Block, 21 Sassoon Road, Hong Kong, Hong Kong aut NATIONALLICENCE 700 1- Sham Pak-Chung Department of Psychiatry, The University of Hong Kong, Hong Kong, Hong Kong aut NATIONALLICENCE 700 1- Kung Annie Department of Medicine, The University of Hong Kong, Lab Block, 21 Sassoon Road, Hong Kong, Hong Kong aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 130/4(2011-10-01), 539-546 0340-6717 130:4<539 2011 130 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer