A Whole-Genome Linkage Scan Suggests Several Genomic Regions Potentially Containing Quantitative Trait Loci for Osteoporosis

Deng, Hong Wen; Xu, Fusheng; Huang, Qihua; Shen, Hui; Deng, Hong‐Wen; Conway, Theresa; Liu, Yong Jun; Liu, Yao Zhong; Li, Jin Long; Zhang, Hai Tao; Davies, K. Michael; Recker, Robert R.

doi:10.1210/jc.2002-020474

Cited by 128 publications

(98 citation statements)

References 65 publications

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“…For instance, the QTL region for femur Ip on Chr 1 is homologous to the region of human Chr 6q25-27, which is linked to spine and trochanter BMD [18]. Syntenic regions corresponding to the QTL regions for femur total area on Chrs 1, 6, 7 and 10 were also linked to wrist bone size on 9q21, forearm and hip BMD on 2p21-25, spine BMD on 22q13, and hip BMD on17p11-12 in humans [9,14,19]. Given the destructive nature of bone strength testing and the lack of statistical power in many human genome-wide linkage studies, it is not surprising that many QTL detected in this study have not been identified in human studies.…”

Section: Discussionmentioning

confidence: 97%

“…Of those, QTL linked to L5 structure, but not femoral structure, were detected on Chrs 2, 12 and 16. Among those being detected, QTL on Chr 7 is particularly worth noting because it not only exhibited the maximum LOD score, but it is homologous to chromosome 12q21 in human, linked to spine BMD [9]. For lumbar structure, d/d allele caused significantly lower genotypic mean values on Chrs 2, 7, 10, 12 and 16, but the opposite trend was observed on Chr 1.…”

Section: Discussionmentioning

confidence: 99%

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Genetic loci affecting bone structure and strength in inbred COP and DA rats

Sun

Alam

Liu

et al. 2008

Bone

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Previous studies have shown that the Copenhagen 2331 (COP) and Dark Agouti (DA) rats have significant differences in bone structure and strength despite their similar body mass. Thus, these inbred rat strains may provide a unique resource to identify the genetics underlying the phenotypic variation in bone fragility. A sample of 828 (405 males and 423 females) COP × DA F2 progeny had extensive phenotyping for bone structure measures including cortical bone area and polar moment of inertia at the femur midshaft and total, cortical and trabecular bone areas, for the lumbar vertebra 5 (L5). Bone strength phenotypes included ultimate force, stiffness and work to failure of femur and L5. These skeletal phenotypes were measured using peripheral quantitative computed tomography (pQCT) and mechanical testing. A whole-genome screen was conducted in the F2 rats, using microsatellite markers spaced at approximately 20 cM intervals. Genetic marker maps were generated from the F2 data and used for genome-wide linkage analyses to detect linkage to the bone structure and strength phenotypes. Permutation testing was employed to obtain the thresholds for genomewide significance (p<0.01). Significant QTL for femur structure and strength were identified on chromosome (Chr) 1 with a maximum LOD score of 33.5; evidence of linkage was found in both the male and female rats. In addition, Chrs 6, 7, 10, 13, 15 and 18 were linked to femur midshaft structure. QTL linked to femur strength were identified on Chrs 5 and 10. For L5 vertebrae, Chrs 2, 16, and 18 harbored QTL for cortical structure and trabecular structure for L5 was linked to Chrs 1, 7, 12, and 18. One female-specific QTL for femur ultimate force was identified on Chr 5, and two male-specific QTL for L5 cortical area were found on Chrs 2 and 18. Our study demonstrates strong evidence of linkage for bone structure and strength to multiple rat chromosomes.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Genetic loci affecting bone structure and strength in inbred COP and DA rats

Sun

Alam

Liu

et al. 2008

Bone

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“…The 17p13 region of the human genome contains quantitative trait loci regulating BMD [9]. This region, which was also identified in an early meta--analysis of genome wide association studies (GWAS) for femoral neck BMD [10], includes the genes encoding arachidonate 12--lipoxygenase (ALOX12) and arachidonate 15--lipoxygenase (ALOX15).…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in inflammation associated genes ALOX15 and IL-6 are associated with bone properties in young women and fracture in elderly

Herlin

McGuigan

Luthman

et al. 2015

Bone

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“…Deng et al (Deng et al, 2002) also reported suggestive evidence (LOD=2.43) for a QTL for spine BMD on 13q33-13q34, but this may represent a different QTL.…”

Section: Discussionmentioning

confidence: 95%

Localization of Quantitative Trait Loci for Bone Mineral Density on Chromosome 13 in the Mongolian Population

Seo¹,

Lim²,

Ahn³

et al. 2009

Genomics & Informatics

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Although the genetic basis for bone mineral density (BMD) has been studied by many groups so far, genes responsible for this complex trait has not been completely revealed. In order to localize quantitative trait loci (QTLs) for BMD variation in Asian population, the study was designed using a group of Mongolian population, a genetically closed population with a homogeneous lifestyle. BMD was measured at the left and right wrists and ankles using DEXA in 1,082 participants from 142 families. Genotyping of 13 polymorphic microsatellite markers on chromosome 13 (average spacing 8-9 cM) and two-point and multipoint linkage analysis were performed. In two-point linkage analysis, we identified two markers, D13S175 (6.03 cM) and D13S265 (68.73 cM) that had LOD scores greater than 1 for left ankle (LOD=2.09, LOD=1.49, respectively). We also found a marker D13S175 (6.03 cM) with a high LOD for left wrist (LOD=1.49) and the markers D13S265 (68.73 cM) and D13S217 (17.21 cM) for the right wrist (LOD= 1.82, LOD= 1.62, respectively). Among these significant marker regions, only two regions at 17 cM (13p11) and 65 cM (13q21) for the right wrist overlapped with major QTLs reported in following multipoint linkage analysis (LOD= 1.7549, LOD=1.4462, respectively). This study provides the possible evidence of the presence of QTLs affecting right wrist BMD in Mongolian populations on 13p11 and 13q21. Modest evidence was also found for genes affecting left ankle and left wrist BMD on 13p13.

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A Whole-Genome Linkage Scan Suggests Several Genomic Regions Potentially Containing Quantitative Trait Loci for Osteoporosis

Cited by 128 publications

References 65 publications

Genetic loci affecting bone structure and strength in inbred COP and DA rats

Genetic loci affecting bone structure and strength in inbred COP and DA rats

Polymorphisms in inflammation associated genes ALOX15 and IL-6 are associated with bone properties in young women and fracture in elderly

Localization of Quantitative Trait Loci for Bone Mineral Density on Chromosome 13 in the Mongolian Population

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