Dual energy x-ray absorptiometry analysis contributes to the prediction of hip osteoarthritis progression

Introduction: To determine if structural bone parameters obtained from dual energy X-ray absorptiometry (DXA) contribute to the prediction of progression of hip osteoarthritis (OA) and to test if the difference between the most affected (OA) hip and the contralateral hip adds to this prediction.Methods: The study group involves a prospective cohort of 189 patients that met the American College of Rheumatology (ARC) classification criteria for hip osteoarthritis. Progression was defined as 20% joint space narrowing or total hip replacement within a two years follow up. Software was developed to calculate geometrical aspects and bone mineral density (BMD) in different regions of interest of the proximal femur. Logistic regression was used to test if Kellgren and Lawrence (K-L) scores and DXA parameters can predict progression of OA. Models were compared using -2log likelihood tests, R2Nagelkerke and areas under the Receiver Operator Characteristic curves, assessed using 10-fold cross validation.Results: The model that included the DXA variables was significantly better in predicting hip OA progression than the model with K-L score of the affected side

Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis

Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10−8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs496547), while the other two (DOT1L and SUPT3H/RUNX2) were previously identified. A systematic prioritization for underlying causal genes was performed using diverse lines of evidence. Exome sequencing data (n = 2,050 individuals) indicated that there were no rare exonic variants that could explain the identified associations. In addition, TGFA, FGFR3 and PIK3R1 were differentially expressed in OA cartilage lesions versus non-lesioned cartilage in the same individuals. In conclusion, we identified four novel loci (TGFA, PIK3R1, FGFR3 and TREH) and confirmed two loci known to be associated with cartilage thickness.The identified associations were not caused by rare exonic variants. This is the first report linking TGFA to human OA, which may serve as a new target for future therapies

Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity

Genome-wide association and functional studies identify a role for IGFBP3 in hip osteoarthritis

International audienc

Colombia diversidad biótica IX : Ciénagas de Córdoba: Biodiversidad ecología y manejo ambiental

ilustraciones, fotografías, gráficas, mapas, tablasLa variabilidad de las ciénagas en el departamento de Córdoba se relaciona con los montos de precipitación en un régimen de distribución unimodal bi-estacional, con valores entre 1000-1500 mm de precipitación anual (ciénagas del complejo grande de Lorica) bajo la influencia del Río Sinú, hasta valores entre > 2500-3000 mm como las de Ayapel y de Arcial bajo la influencia del Río San Jorge. Las ciénagas del río Sinú (charco Pescao, Bañó, Pantano Bonito) presentan una mayor eutrofización (nutrientes, materia orgánica) que las del San Jorge (El Porro, Cintura, Arcial) y en general hubo mayores recuentos de bacterias indicadoras de contaminación, que se incrementaron durante la época lluviosa. En el zooplancton predominan los rotíferos, seguidos por las fases juveniles de los copépodos, cladóceros y copépodos adultos. El establecimiento de la vegetación acuática esta relacionado con la cantidad de sólidos suspendidos en el agua, en aguas transparentes como Arcial, Cintura, Charco pescao hay elementos acuáticos sumergidos, enraizados emergentes y flotantes con los tapetes de Eichhornia crassipes. La vegetación de pantano está conformada por diferentes ensambles dominados por especies de Cyperaceae y Polygonaceae. En la vegetación de ribera son importantes los matorrales de mangle (Symmeria paniculata). La vegetación acuática y la de la llanura aluvial son las responsables del aporte de materia orgánica a la cubeta en el proceso anual de aguas altas y bajas. En el sedimento se encontraron representantes de Nematodos, Anélidos, Moluscos y Artrópodos y una concentración de materia orgánica relativamente baja, respecto al valor (%) de materia mineral. La vegetación de los bosques alrededor de los ciénagas se reúne en la gran formación dominada por Crateva tapia y Astronium graveolens, incluye diferentes bosques que cuentan entre sus elementos característicos y dominantes a Cavanillesia platanifolia, Bursera simarouba, Cochlospermum vitifolium, Apiba aspera, Cariniana pyriformis, Guazuma ulmifolia, Tapirira guianensis, Samanea saman, y Tabebuia rosea. En el paisaje son muy vistosos los palmares de Sabal mauritiformis, Bactris guianensis, Oenocarpus mapora y O. bataua. La riqueza de la flora se cifra en 1000 especies de plantas vasculares con mayor diversidad en las familias Fabaceae, Rubiaceae, Mimosaceae y Poaceae, patrón distintivo de la riqueza de las tierras bajas de Colombia. La fauna asociada a las ciénagas incluye 47 especies de reptiles, 39 del orden Squamata (Lagartos 46% y Serpientes 54%), una perteneciente al orden Crocodylia y siete al orden Testudinata (tortugas). Se registraron 49 especies de mamíferos, algunos grandes pertenecientes a los órdenes Carnívora, Primates, Phyllophaga (osos perezosos) y Vermilingua (osos hormigueros). Se registraron 180 especies de aves de 51 familias, con la mayor representatividad en Tyrannidae. Las ciénagas de Lorica y El Porro albergan grandes grupos de especies acuáticas, especialmente de las familias Ardeidae, Anatidae y Rallidae. No obstante la fuente importante de riqueza natural de las ciénagas y su entorno, la situación socioeconómica de la mayor parte del campesinado es crítica. Esta población necesita ayuda urgente del gobierno a nivel de inversiones y planes de desarrollo, en los cuales es fundamental considerar el capital natural que significa la biodiversidad de las ciénagas y la necesaria utilización de los servicios ambientales que prestan local, regional y nacionalmente estos ambientes siempre y cuando se les conserve. (Texto tomado de la fuente).ISBN de la versión impresa: 9789587194067Incluye anexosPrimera edició

Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis

Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10−8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs496547), while the other two (DOT1L and SUPT3H/RUNX2) were previously identified. A systematic prioritization for underlying causal genes was performed using diverse lines of evidence. Exome sequencing data (n = 2,050 individuals) indicated that there were no rare exonic variants that could explain the identified associations. In addition, TGFA, FGFR3 and PIK3R1 were differentially expressed in OA cartilage lesions versus non-lesioned cartilage in the same individuals. In conclusion, we identified four novel loci (TGFA, PIK3R1, FGFR3 and TREH) and confirmed two loci known to be associated with cartilage thickness.The identified associations were not caused by rare exonic variants. This is the first report linking TGFA to human OA, which may serve as a new target for future therapies

Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis.

Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10-8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs496547), while the other two (DOT1L and SUPT3H/RUNX2) were previously identified. A systematic prioritization for underlying causal genes was performed using diverse lines of evidence. Exome sequencing data (n = 2,050 individuals) indicated that there were no rare exonic variants that could explain the identified associations. In addition, TGFA, FGFR3 and PIK3R1 were differentially expressed in OA cartilage lesions versus non-lesioned cartilage in the same individuals. In conclusion, we identified four novel loci (TGFA, PIK3R1, FGFR3 and TREH) and confirmed two loci known to be associated with cartilage thickness.The identified associations were not caused by rare exonic variants. This is the first report linking TGFA to human OA, which may serve as a new target for future therapies

Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus

Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged > 55 years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p 1.25) may still be consistent with an effect size < 1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures