Tim D Spector

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..abstract:..

..Osteoporosis is diagnosed by the measurement of bone mineral density, which is a highly heritable and multifactorial trait. We aimed to identify genetic loci that are associated with bone mineral density...

..Additional discovery of both common and rare variants will yield further etiological insight and accelerate clinical applications...

..The aim of this study was to show that skeletal ratios, such as length of femur to height, could be accurately measured from a DXA (dual energy X-ray absorptiometry) image...

..Genetic variation can affect the innate immune response to certain environmental factors, and may, therefore, determine an individual's lifetime risk of disease...

..The objective of this study was to examine the relationship between common genetic variation of the ESR2 gene and osteoarthritis...

..Bone mineral density (BMD) is a useful surrogate marker for risk of fracture and is a highly heritable trait. The genetic variants underlying this genetic contribution are largely unknown...

..Such discordant monozygotic twin pairs are rare and very few studies have explored the potential usefulness of this approach...

..This study adds to the weight of evidence suggesting that side effect profiles of MMP inhibitors in general make them unsuitable for use in osteoarthritis...

..6 or greater for assessing JSN over three years. Selecting a single reader was the most accurate method, with 0.3 mm precision. Using this cutoff, 50% of patients were classified as 'progressors'...

..Both doses of risedronate were well tolerated. In this study, clear trends towards improvement were observed in both joint structure and symptoms in patients with primary knee OA treated with risedronate...

..The effect of oral choline-stabilized orthosilicic acid (ch-OSA) on markers of bone turnover and bone mineral density (BMD) was investigated in a double-blind placebo-controlled trial...

..Clinical studies are now under way to determine the efficacy and safety of bisphosphonates which may offer new therapeutic options in the treatment of OA...

..OA is a complex disease, and understanding its complexity should help us find the genes and new pathways and drug targets...

..The resource has led to many successful and innovative research projects particularly in common age-related diseases, and has led to collaborations with over 80 groups worldwide...

..The registry has led to many successful innovative research projects, particularly in common diseases previously thought to be predominantly environmental and helped positionally clone some novel genes for common diseases...

..To perform a large-scale association analysis of single-nucleotide polymorphisms (SNPs) in patients with radiographically defined osteoarthritis (OA) of the knee...

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..To assess whether the association of genetic polymorphisms with osteoarthritis (OA) in other populations could be replicated in a large, multicenter, mixed-sex, case-control study of clinical knee OA...

..The aims of the current study from the EU consortium EuroCLOT were to (1) determine the heritability of fibrin phenotypes and (2) identify QTLs associated with fibrin phenotypes...

..We therefore tested the hypothesis that physical activity level in leisure time (over the past 12 months) is associated with leukocyte telomere length (LTL) in normal healthy volunteers...

..To examine the relative roles of genetic and environmental factors in central retinal thickness, by performing a classical twin study...

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..To assess the genetic association of pain in patients with knee osteoarthritis (OA) and those with multiple regional pain with the R1150W variant in the α-subunit of the voltage-gated sodium channel Na(V)1.7...

..If SH2-B signaling is attenuated in diet-induced obesity, it could become a target for drug-induced leptin sensitization...

..07). The rs10947262 and rs7775228 variants are not associated with risk of knee OA in European descent populations and they do not appear tag the same HLA class II haplotype as they do in Japanese individuals...

..This study used a classical twin design to examine whether these conditions are linked through shared environmental exposures or by a common underlying genetic propensity to vasospasm...

..Leukocyte telomere length (LTL) is a predictor of aging-related disease and decreases with each cell cycle and increased inflammation...

..Understanding mechanisms influencing the induction and involution of nevi will not only help in understanding the pathophysiology of melanoma but should also shed light on the complex relationship between aging and cancer...

..We undertook this study to test whether genetic variation at ANP32A was associated with osteoarthritis (OA) in women...

..PTPN1 variants appear to contribute to central fat and metabolic syndrome traits, secondary to their effect on insulin sensitivity...

..That two mitochondrial regulatory processes in the retina are implicated in the aetiology of myopia is surprising and is likely to provide novel insight into the molecular genetic basis of common myopia...

..Replication and further fine mapping of this region is ongoing to determine potential genes influencing bone size and diseases affecting bone...

..We undertook this study to investigate the role of genetic variation in SMAD3 in the risk of large-joint OA in humans...

..Our results and previous studies on the role of the cyclooxygenase 2 enzyme encoded by PTGS2 underscore the importance of this signaling pathway in the pathogenesis of knee OA...

..This large twin study aimed to explore the role of shared environment in refractive error...

..This classic twin study was designed to determine the heritability of macular pigment (MP) augmentation in response to supplemental lutein (L) and zeaxanthin (Z)...

..The recent nonlinear computer version of homeostasis model assessment (HOMA)2 provides an appropriate and convenient assessment of glucose metabolism, enabling gene-mapping studies in large population samples...

..We assessed hypermobility and its relationship to bone mineral density (BMD) and OA in a postmenopausal female community population...

..The nature of the association is unclear, but such an association implies that, in managing BMD loss, women might benefit from maintaining a high level of DHEAS...

..5×10(-14)) and also at VRII (p = 2×10(-4)) suggesting a possible predisposing role for this site in the accumulation of heteroplasmy. Our data indicate that BMI is potentially associated with control region heteroplasmy...

..An association between COMP and OA has been shown, yet the precise factors governing serum levels of COMP remain unclear. The aim of this study was to determine whether genetic factors influence serum levels of COMP...

..9) at 14q23.2, and suggestive linkage at 10q26.13 (LOD 2.4) and 3p26.1 (LOD 2.7). This is the first report of loci, mapped in a sample of healthy individuals, that influence mean telomere variation in humans...

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..The current study investigated 6 single-nucleotide polymorphisms (SNPs) within the FXIII A-subunit gene to locate functional polymorphism(s) responsible for variation in FXIII activation...

..76, empirical p-value 0.0006). Within this QTL lies an obvious candidate-the SCAD gene. These results suggest that large-scale gene discovery studies are possible with self-report memory questionnaires...

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..2 kb of the ADIPOQ promoter region was cloned in a luciferase reporter plasmid, and the four haplotypes were transfected in differentiated 3T3-L1 adipocytes. No significant allelic effects on promoter activity were found...

..This finding has important implications for future studies investigating MPOD, and its response to dietary modification/supplementation...

..59) between these two traits and to assess the shared and specific influence of established and novel cardiovascular disease risk factors on them...

..Cross-sectional LDD as determined by MRI scan is known to be highly heritable. The authors postulated that the rate of progression might also be controlled by genetic factors...

..This was a cohort study in which 344 pairs of twins, 163 monozygotic (MZ) and 181 dizygotic (DZ), were enrolled...

..Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS...

..To estimate the genetic influence on joint hypermobility in an unselected population using a classic twin study design...

..Telomere loss in white blood cells (WBC) is accelerated by oxidative stress and inflammation in vitro. It was postulated that the accelerated WBC telomere shortening in RA occurs as a result of exposure to chronic inflammation...

..We examined the role of 26 single-nucleotide polymorphisms (SNPs) from 24 candidate genes in OA susceptibility and progression...

..CONCLUSIONS: Our results suggest a role for genes regulating inflammatory pathways in the radiographic progression of spine degeneration. This could prove a fruitful area for future therapeutics for the spine and other joints...

..The goal of this study was to examine the progression of central arterial pulse pressure (cPP) in women and the degree to which this can be reversed by nitrovasodilation...

..To assess if a coding variant in the gene encoding transient receptor potential cation channel, subfamily V, member 1 (TRPV1) is associated with genetic risk of painful knee osteoarthritis (OA)...

..BMD is highly heritable, but statistical models showed very little overlap of shared genes between the two traits...

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..Therefore, this is likely to be the first reported classical twin study...

..There is a pressing need to develop reliable molecular biomarkers in osteoarthritis. The aim of the study was to identify novel serum biomarkers for osteoarthritis using a metabolomics approach...

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..The aims of this study were to estimate heritability of the ratio of measured FEV1 (mFEV1) to expected FEV(1) (eFEV1) in a white population, and to examine the interaction between genetic factors and smoking on this ratio...

..They provide both novel and replicated QTLs for nevus development, some of which might overlap with those for melanoma and warrant detailed investigation...

..However the current study design does not preclude the possibility of confounding between heritability estimates and unobserved prenatal effects...

..Genetic influences were found for all SOS and BMD measurements. A combination of shared and unique genetic influences was found to control BMD and SOS at the radius...

..Public health messages are advocating sun avoidance to reduce skin cancer risk but the potential deleterious effects of these recommendations for vitamin D metabolism have been poorly investigated...

..Patterns of food intake and prevalent osteoarthritis of the hand, hip, and knee were studied using the twin design to limit the effect of confounding factors. Compounds found in associated food groups were further studied in vitro...

..46) despite substantial differences in average ancestry. The data confirm ethnic differences in FC levels and indicate the potential usefulness of these populations for admixture mapping of genes for FC levels...

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..FOD has been acknowledged to be multifactorial and recent research has implicated the importance of psychosocial risk factors...

..High BMD at non-joint sites is associated with an increased risk of OA; however, low BMD and high bone turnover appears to be associated with more rapid progression. These alterations in bone turnover offer new therapeutic opportunities...

..g., learning to use a new gadget). Given their clinical significance and ease of administration, these tests could prove to be useful in examining memory functioning in large-scale population studies...

..To examine the roles of genetic and environmental factors in corneal hysteresis and ocular pulse amplitude by performing a classic twin study...

..The scope of the present article is to offer an overview of recent developments in the genetic epidemiology of knee and hip osteoarthritis, with particular emphasis on published genomewide association studies (GWAS)...

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..Future studies should focus on the fine mapping of these replicated regions, which include potential candidate genes...

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..78 (P<0.0001)). Associations of BMI, weight and total fat with SNPs in regions flanking the POMC gene in this powerful study suggest that regulation of POMC expression may be influential in determining body weight...

..CONCLUSIONS: This classic twin study demonstrates that genetic background is an important determinant of MP optical density, reflected in heritability estimates of 0.67 and 0.85 for HFP and AF measures, respectively...

..In contrast to the successful advances of genetic research in a wide variety of human diseases, genetic exploration in FSD lags far behind...

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..001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior...

..It seems that the most important targets for intervention and prevention occur outside of the family, such as relationship quality and satisfaction, and history of abuse...

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..This study was undertaken to examine the association of bone mass with incident and progressive disease and to determine whether prior fractures influence the development of OA...

..Although a putative mechanism of action suggests a disease-modifying effect, the important outcomes from this trial are good symptom response and a low adverse effect profile, albeit in the small number of patients studied...

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..The results support a key role for the HBS1L-related genetic variants in HbF control and illustrate the biological complexity of the mechanism of 6q QTL as a modifier of fetal hemoglobin levels in the beta hemoglobinopathies...

..Some female sexual problems have been reported to cluster with psychological and social problems. Underlying personality type may play a role in the development or maintenance of such problems...

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..0067) and P2RX4 (P = 0.017). These data provide replication and refinement of the 12q24 obesity locus and suggest that genes involved in phospholipase and purinoreceptor pathways may regulate fat accumulation and distribution...

..Leukocyte telomere length is inversely correlated with age, insulin resistance, serum leptin, and smoking...

..In contrast, somatization was shown to be moderately heritable. CONCLUSION: Genetic factors are of little or no influence on IBS where the predominant influences appear to be environmental...