114 research outputs found
(E)-N′-[(E)-3-(4-Hydroxy-3-methoxyphenyl)allylidene]isonicotinohydrazide
In the title compound, C16H15N3O3, the dihedral angle between the pyridine and benzene rings is 7.66 (5)°. The crystal packing is consolidated by intermolecular C—H⋯O and O—H⋯N interactions, which link the molecules into zigzag chains propagating along [010]. The chains are further linked into a three-dimensional network by N—H⋯O, C—H⋯N, C—H⋯O and C—H⋯π interactions
Monoclinic polymorph of poly[aqua(μ4-hydrogen tartrato)sodium]
A monoclinic polymorph of the title compound, [Na(C4H5O6)(H2O)]n, is reported and complements an orthorhombic form [Kubozono, Hirano, Nagasawa, Maeda & Kashino (1993 ▶). Bull. Chem. Soc. Jpn, 66, 2166–2173]. The asymmetric unit contains a hydrogen tartrate anion, an Na+ cation and a water molecule. The Na+ ion is surrounded by seven O atoms derived from one independent and three symmetry-related hydrogen tartrate anions, and a water molecule, forming a distorted pentagonal–bipyramidal geometry. Independent units are linked via a pair of intermolecular bifurcated O—H⋯O acceptor bonds, generating an R
2
1(6) ring motif to form polymeric two-dimensional arrays parallel to the (100) plane. In the crystal packing, the arrays are linked by adjacent ring motifs, together with additional intermolecular O—H⋯O interactions, into a three-dimensional network
Triethylammonium 4-nitrobenzenesulfonate
In the anion of the title molecular salt, C6H16N+·C6H4O5S−, the nitro group is twisted slightly from the benzene ring, making a dihedral angle of 3.16 (10)°. In the crystal structure, the cations and anions are linked into a two-dimensional network parallel to the ab plane by C—H⋯O and N—H⋯O hydrogen bonds
1,3-Bis[(3-allylimidazol-3-ium-1-yl)methyl]benzene bis(hexafluoridophosphate)
In the title compound, C20H24N4
2+·2PF6
−, the ethene and 3-allylimidazolium moieties of the cation are disordered over two positions with refined site occupancies of 0.664 (19):0.336 (19) and 0.784 (7):0.216 (7), respectively, whereas four F atoms of one hexafluoridophosphate anion and all atoms in the other hexafluoridophosphate anion are disordered over two positions with refined site occupancies of 0.764 (5):0.2365) and 0.847 (9):0.153 (9), respectively. The benzene ring is inclined at angles of 78.2 (3), 81.3 (4) and 73.9 (12)° with the 1H-imidazol-3-ium ring and the major and minor components of the disordered 1H-imidazol-3-ium ring, respectively. In the crystal, the hexafluoridophosphate anions link the cations into two-dimensional networks parallel to (001) via intermolecular C—H⋯F hydrogen bonds. The crystal structure is further consolidated by π–π [centroid–centroid distance = 3.672 (3) Å] and C—H⋯π interactions
2-{[5-(Adamantan-1-yl)-4-methyl-4H-1,2,4-triazol-3-yl]sulfanyl}-N,N-dimethylethanamine
In the title compound, C17H28N4S, the 1,2,4-triazole ring is nearly planar [maximum deviation = 0.005 (2) Å]. There are no significant hydrogen bonds observed in the crystal structure. The crystal studied was a non-merohedral twin, the refined ratio of twin components being 0.281 (3):0.719 (3)
Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects.
Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course
Assessment of gene-by-sex interaction effect on bone mineral density
To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p < 1 × 10(-5) ) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect = 0.02 and p = 3.0 × 10(-5) ; female effect = -0.007 and p = 3.3 × 10(-2) ), and 11 suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (p < 5 × 10(-8) ) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found to influence BMD variation in this screen of autosomal markers. If they exist, gene-by-sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP. © 2012 American Society for Bone and Mineral Research.Medtronic
NIH R01 AG18728
R01HL088119
R01AR046838
U01 HL084756
R01 AR43351
P01-HL45522
R01-MH-078111
R01-MH-083824
Nutrition and Obesity Research Center of Maryland P30DK072488
NIAMS/NIH F32AR059469
Instituto de Salud Carlos III-FIS (Spanish Health Ministry) PI 06/0034
PI08/0183
Canadian Institutes of Health Research (CIHR)
NHLBI HHSN268201200036C
N01-HC-85239
N01-HC-85079
N01-HC-85086
N01-HC-35129
N01 HC15103
N01 HC-55222
N01-HC-75150
N01-HC-45133
HL080295
HL087652
HL105756
NIA AG-023629
AG-15928
AG-20098
AG-027058
N01AG62101
N01AG62103
N01AG62106
1R01AG032098-01A1
National Center of Advancing Translational Technologies CTSI UL1TR000124
National Institute of Diabetes and Digestive and Kidney Diseases DK063491
EUROSPAN (European Special Populations Research Network)
European Commission FP6 STRP grant 018947
LSHG-CT-2006-01947
Netherlands Organisation for Scientific Research
Erasmus MC
Centre for Medical Systems Biology (CMSB)
Netherlands Brain Foundation (HersenStichting Nederland)
US National Institute for Arthritis, Musculoskeletal and Skin Diseases
National Institute on Aging R01 AR/AG41398
R01 AR050066
R21 AR056405
National Heart, Lung, and Blood Institute's Framingham Heart Study N01-HC-25195
Affymetrix, Inc. N02-HL-6-4278
Canadian Institutes of Health Research from Institute of Aging 165446
Institute of Genetics 179433
Institute of Musculoskeletal health 221765
Intramural Research Program of the NIH, National Institute on Aging
National Institutes of Health HHSN268200782096C
Hong Kong Research Grant Council HKU 768610M
Bone Health Fund of HKU Foundation
KC Wong Education Foundation
Small Project Funding 201007176237
Matching Grant
CRCG Grant
Osteoporosis and Endocrine Research Fund
Genomics Strategic Research Theme of The University of Hong Kong
Netherlands Organisation of Scientific Research NWO Investments 175.010.2005.011
911-03-012
Research Institute for Diseases in the Elderly 014-93-015
Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) 050-060-810
Erasmus Medical Center and Erasmus University, Rotterdam
Netherlands Organization for the Health Research and Development (ZonMw)
Research Institute for Diseases in the Elderly (RIDE)
Ministry of Education, Culture and Science
Ministry for Health, Welfare and Sports
European Commission (DG XII)
Municipality of Rotterdam
German Bundesministerium fur Forschung und Technology 01 AK 803 A-H
01 IG 07015
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
New genetic loci link adipose and insulin biology to body fat distribution.
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms
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