Linkage and Association for Bone Mineral Density and Heel Ultrasound Measurements with a Simple Tandem Repeat Polymorphism near the Osteocalcin Gene in Female Dizygotic Twins

Andrew, Toby; Mak, Y. T.; Reed, P.; Macgregor, Alexander; Spector, TD

doi:10.1007/s001980200102

Cited by 16 publications

(9 citation statements)

References 28 publications

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“…Investigations included several questionnaires inquiring about present and past diseases, symptoms, family history, socio-economical factors, and medication. Subjects underwent an extensive clinical assessment including DEXA measurements of bone mineral density and anthropometric measurements [17,24]. All individuals with data on lumbar spine BMD were considered for inclusion.…”

Section: Methodsmentioning

confidence: 99%

Association between a variation in the phosphodiesterase 4D gene and bone mineral density

et al. 2005

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Section: Methodsmentioning

confidence: 99%

Association between a variation in the phosphodiesterase 4D gene and bone mineral density

et al. 2005

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“…There is less power to detect linkage on chromosome X, because identity by descent allele sharing only ranges from 0 to 1 instead of 0‐2 as in autosomes, suggesting the possibility of a QTL with a large effect at Xq28. Of these genomic regions, the 1q21‐24, 2q33‐37, and 4q12‐21 intervals have been highlighted in previous studies as potentially important for studies of bone QTL (12, 23‐26) . The BUA peaks on chromosome 2 at 215 and 240 may overlap weak linkage peaks for lumbar spine BMD (LOD 1.3‐1.42) at 203 and 221 cM (Fig.…”

Section: Discussionmentioning

confidence: 90%

“…The linkage for VOS and BUA at 1q21–24 contains candidate genes such as bone γ‐carboxyglutamate (gla) protein (osteocalcin), interleukin 6 receptor, and lamin A/C. Genetic variation in osteocalcin has previously been reported to be associated with variation in BUA and hip BMD (23‐26) . Whether an association exists with polymorphisms in other known or other novel genes in the region remains to be defined.…”

Section: Discussionmentioning

confidence: 99%

A Genome-Screen of a Large Twin Cohort Reveals Linkage for Quantitative Ultrasound of the Calcaneus to 2q33–37 and 4q12–21

Wilson

Reed

Andrew

et al. 2004

Journal of Bone and Mineral Research

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A genome-wide screen was performed on a large cohort of dizygous twin pairs to identify regions of the genome that contain QTL for QUS of bone. Suggestive linkage of QUS parameters to 2q33-37 and 4q12-21 highlighted these regions as potentially important for studies of genes that regulate bone. Introduction:The genetics of osteoporotic fracture is only partly explained by bone mineral density (BMD). Quantitative ultrasound (QUS) of the calcaneus can also be used for independent clinical assessment of osteoporotic fracture risk. Two specific indices are derived from this assessment: broadband ultrasound attenuation (BUA) and velocity of sound (VOS). Both parameters provide information on fracture risk; however, BUA has been studied more extensively and may be favored because it is thought to have a stronger predictive value for osteoporotic fracture and incorporates aspects of trabecular structure and bone quality as well as BMD. Studies of QUS in twins have shown that both derived parameters are under substantial genetic control, independent of BMD. Materials and Methods: To identify regions of the genome that contain quantitative trait loci (QTL) for QUS of bone, we performed a genome-wide screen on a large cohort of dizygous twin pairs. Unselected female dizygous twins from 1067 pedigrees from the St Thomas' UK Adult Twin Registry were genome scanned (737 highly polymorphic microsatellite markers). Multipoint linkage analyses provided maximum evidence of linkage for BUA (LOD 2.1-5.1) to 2q33-37. Linkage for VOS (LOD 2.2-3.4) was maximal at 4q12-21. Potential evidence of linkage in the cohort indicated five other possible locations of QTL (LOD Ͼ2.0) relevant to bone density or structure on chromosomes 1, 2, 13, 14, and X. Results and Conclusions: This study has identified eight genomic locations with linkage of LOD Ͼ2.0. This data should be of value in assisting researchers to localize genes that regulate bone mass and microstructure. These results should complement genome screens of BMD and bone structure and serve to enable further targeted positional candidate and positional cloning studies to advance our understanding of genetic control of bone quality and risk of fracture.

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“…A limitation of current model fitting methods (Van den Oord and Snieder 2002; Van den Oord et al 2004;Andrew et al 2002) is that first all alternative models have to be specified, then they need to be fitted to the data, and finally all the fit indices need to be compared to select the best fitting model. This becomes impossible in data sets where many measured genetic variants and clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

Genetics and diagnostic refinement

et al. 2006

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For many psychiatric conditions it is speculated that, rather than being single disease entities, they are a set of several disorders sharing clinical features but having (partly) different underlying causes. The possibility of measuring genetic variation on a large scale has given researchers new hope of identifying these disease subtypes that may differ with respect to prognosis, course, and response to treatment. However, although a considerable number of articles have been published suggesting that we may even be on the verge of making genotype-based diagnoses, the reality is that we do not have a good answer to even the most basic question of how measured genes could best be used to refine diagnostic categories. In this article, we show that for common psychiatric disorders, it may not be possible to simply look for similar genetic profiles in groups of patients. Instead, we propose a model assuming that genotypes affect phenotypes through more or less coherent etiological systems or pathogenic processes and argue that these etiological systems may provide a more fruitful basis for defining disease subtypes. Several examples from the literature that support the face validity of different aspects of our model are given. Finally, we argue that, given our limited knowledge of disease etiology, the use of discovery-oriented techniques requiring extensive data collection and (artificial) intelligent computer searches may be imperative, and discuss the prospect of model-based diagnosis to classify etiologically different disease subtypes.

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Linkage and Association for Bone Mineral Density and Heel Ultrasound Measurements with a Simple Tandem Repeat Polymorphism near the Osteocalcin Gene in Female Dizygotic Twins

Cited by 16 publications

References 28 publications

Association between a variation in the phosphodiesterase 4D gene and bone mineral density

Association between a variation in the phosphodiesterase 4D gene and bone mineral density

A Genome-Screen of a Large Twin Cohort Reveals Linkage for Quantitative Ultrasound of the Calcaneus to 2q33–37 and 4q12–21

Genetics and diagnostic refinement

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