| 1. |
|
|
| 2. |
|
|
| 3. |
- Yusuf, D, et al.
(författare)
-
The transcription factor encyclopedia
- 2012
-
Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906. ; 13:3, s. R24-
-
Tidskriftsartikel (refereegranskat)
|
|
| 4. |
- Sen, Partha, et al.
(författare)
-
Novel FOXF1 Mutations in Sporadic and Familial Cases of Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins Imply a Role for its DNA Binding Domain
- 2013
-
Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794. ; 34:6, s. 801-811
-
Tidskriftsartikel (refereegranskat)abstract
- Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and 10 deletions, we have identified an additional 38 novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, 20 missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic. We report four familial cases of which three show maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA-binding domain, indicating its plausible role in FOXF1 function. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis.
|
|
| 5. |
- Estrada, Karol, et al.
(författare)
-
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
-
Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
|
|
| 6. |
- Oei, L., et al.
(författare)
-
Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus
- 2014
-
Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 59, s. 20-27
-
Tidskriftsartikel (refereegranskat)abstract
- Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fracture 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<5 x 10(-8). In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p = 4.6 x 10(-8). However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% Cl: 0.98-1.14; p = 0.17), displaying high degree of heterogeneity (I-2= 57%; Q(het)p = 0.0006). Under Han-Eskin alternative random effects model the summary effect was significant (p = 0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >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. (C) 2013 Elsevier Inc. All rights reserved.
|
|
| 7. |
|
|
| 8. |
- Frasinski, L. J., et al.
(författare)
-
Dynamics of Hollow Atom Formation in Intense X-Ray Pulses Probed by Partial Covariance Mapping
- 2013
-
Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 111:7, s. 073002-
-
Tidskriftsartikel (refereegranskat)abstract
- When exposed to ultraintense x-radiation sources such as free electron lasers (FELs) the innermost electronic shell can efficiently be emptied, creating a transient hollow atom or molecule. Understanding the femtosecond dynamics of such systems is fundamental to achieving atomic resolution in flash diffraction imaging of noncrystallized complex biological samples. We demonstrate the capacity of a correlation method called partial covariance mapping'' to probe the electron dynamics of neon atoms exposed to intense 8 fs pulses of 1062 eV photons. A complete picture of ionization processes competing in hollow atom formation and decay is visualized with unprecedented ease and the map reveals hitherto unobserved nonlinear sequences of photoionization and Auger events. The technique is particularly well suited to the high counting rate inherent in FEL experiments.
|
|
| 9. |
|
|
| 10. |
- Zhaunerchyk, Vitali, et al.
(författare)
-
Using covariance mapping to investigate the dynamics of multi-photon ionization processes of Ne atoms exposed to X-FEL pulses
- 2013
-
Ingår i: Journal of Physics B. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 46:16, s. 164034-
-
Tidskriftsartikel (refereegranskat)abstract
- We report on a detailed investigation into the electron emission processes of Ne atoms exposed to intense femtosecond x-ray pulses, provided by the Linac Coherent Light Source Free Electron Laser (FEL) at Stanford. The covariance mapping technique is applied to analyse the data, and the capability of this approach to disentangle both linear and nonlinear correlation features which may be hidden on coincidence maps of the same data set is demonstrated. Different correction techniques which enable improvements on the quality of the spectral features extracted from the covariance maps are explored. Finally, a method for deriving characteristics of the x-ray FEL pulses based on covariance mapping in combination with model simulations is presented.
|
|
| 11. |
- Moayyeri, Alireza, et al.
(författare)
-
Genetic determinants of heel bone properties : genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium
- 2014
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:11, s. 3054-3068
-
Tidskriftsartikel (refereegranskat)abstract
- Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
|
|
| 12. |
- Oei, Ling, et al.
(författare)
-
A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus
- 2014
-
Ingår i: Journal of Medical Genetics. - : BMJ Publishing Group. - 0022-2593 .- 1468-6244. ; 51:2, s. 122-131
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk.AIM: To identify CNVs associated with osteoporotic bone fracture risk.METHOD: We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies.RESULTS: A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p=8.69×10(-5)). We performed an in silico meta-analysis in four studies with CNV microarray data and the association with fracture risk was replicated (OR 3.11, 95% CI 1.01 to 8.22; p=0.02). The prevalence of this deletion showed geographic diversity, being absent in additional samples from Australia, Canada, Poland, Iceland, Denmark, and Sweden, but present in the Netherlands (0.34%), Spain (0.33%), USA (0.23%), England (0.15%), Scotland (0.10%), and Ireland (0.06%), with insufficient evidence for association with fracture risk.CONCLUSIONS: These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.
|
|
| 13. |
- Xavier, Prince K., et al.
(författare)
-
Variability of Indian summer monsoon in a new upper tropospheric humidity data set
- 2010
-
Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 37:5, s. L05705-
-
Tidskriftsartikel (refereegranskat)abstract
- Using a new data set we demonstrate the variability of upper troposphere humidity (UTH) associated with the Indian Summer Monsoon (ISM). The main advantage of the new data set is its all-sky representation which is essential to capture the full variability of humidity even in cloudy areas. We show that UTH undergoes significant variations during the active/break phases of the monsoon and discuss the mechanisms. The interannual variations of monsoon are also well reflected in the UTH. A preliminary investigation into the cause of the 2009 monsoon failure reveals anomalous subsidence and suppressed convection over the monsoon region due to anomalous warm conditions in the equatorial Pacific throughout the summer. The large scale drying of the upper troposphere may also have contributed to a negative feedback in suppressing convection. Citation: Xavier, P. K., V. O. John, S. A. Buehler, R. S. Ajayamohan, and S. Sijikumar (2010), Variability of Indian summer monsoon in a new upper tropospheric humidity data set
|
|
| 14. |
|
|
| 15. |
- Fang, L., et al.
(författare)
-
Multiple Ionization and Double Core-hole Production in Molecules using the LCLS X-ray FEL
- 2012
-
Ingår i: Journal of Physics, Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 388:3, s. 032028-
-
Tidskriftsartikel (refereegranskat)abstract
- We used the world's first hard x-ray FEL to investigate the response of molecular systems to the ultra-intense, femtosecond x-ray radiation. We report sequential multiphoton ionization, frustrated absorption and double core hole production mechanisms.
|
|
| 16. |
- Hong, Mun-Gwan, et al.
(författare)
-
A genome-wide assessment of variability in human serum metabolism
- 2013
-
Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 34:3, s. 515-524
-
Tidskriftsartikel (refereegranskat)abstract
- The study of the genetic regulation of metabolism in human serum samples can contribute to a better understanding of the intermediate biological steps that lead from polymorphism to disease. Here, we conducted a genome-wide association study (GWAS) to discover metabolic quantitative trait loci (mQTLs) utilizing samples from a study of prostate cancer in Swedish men, consisting of 402 individuals (214 cases and 188 controls) in a discovery set and 489 case-only samples in a replication set. A global nontargeted metabolite profiling approach was utilized resulting in the detection of 6,138 molecular features followed by targeted identification of associated metabolites. Seven replicating loci were identified (PYROXD2, FADS1, PON1, CYP4F2, UGT1A8, ACADL, and LIPC) with associated sequence variants contributing significantly to trait variance for one or more metabolites (P = 10(-13) -10(-91)). Regional mQTL enrichment analyses implicated two loci that included FADS1 and a novel locus near PDGFC. Biological pathway analysis implicated ACADM, ACADS, ACAD8, ACAD10, ACAD11, and ACOXL, reflecting significant enrichment of genes with acyl-CoA dehydrogenase activity. mQTL SNPs and mQTL-harboring genes were over-represented across GWASs conducted to date, suggesting that these data may have utility in tracing the molecular basis of some complex disease associations.
|
|
| 17. |
- Lambert, J-C, et al.
(författare)
-
Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease
- 2013
-
Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 18:4, s. 461-470
-
Tidskriftsartikel (refereegranskat)abstract
- Recently, several genome-wide association studies (GWASs) have led to the discovery of nine new loci of genetic susceptibility in Alzheimer's disease (AD). However, the landscape of the AD genetic susceptibility is far away to be complete and in addition to single-SNP (single-nucleotide polymorphism) analyses as performed in conventional GWAS, complementary strategies need to be applied to overcome limitations inherent to this type of approaches. We performed a genome-wide haplotype association (GWHA) study in the EADI1 study (n = 2025 AD cases and 5328 controls) by applying a sliding-windows approach. After exclusion of loci already known to be involved in AD (APOE, BIN1 and CR1), 91 regions with suggestive haplotype effects were identified. In a second step, we attempted to replicate the best suggestive haplotype associations in the GERAD1 consortium (2820 AD cases and 6356 controls) and observed that 9 of them showed nominal association. In a third step, we tested relevant haplotype associations in a combined analysis of five additional case-control studies (5093 AD cases and 4061 controls). We consistently replicated the association of a haplotype within FRMD4A on Chr.10p13 in all the data set analyzed (OR: 1.68; 95% CI: (1.43-1.96); P=1.1 x 10(-10)). We finally searched for association between SNPs within the FRMD4A locus and A beta plasma concentrations in three independent non-demented populations (n = 2579). We reported that polymorphisms were associated with plasma A beta 42/A beta 40 ratio (best signal, P=5.4 x 10(-7)). In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD.
|
|
| 18. |
- Larsson, Mats, et al.
(författare)
-
Double core-hole formation in small molecules at the LCLS free electron laser
- 2013
-
Ingår i: Journal of Physics B. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 46:16, s. 164030-
-
Tidskriftsartikel (refereegranskat)abstract
- We have investigated nonlinear processes in small molecules by x-ray photoelectron spectroscopy using the Linac Coherent Light Source free electron laser, and by simulations. The main focus of the experiments was the formation of the two-site double core-hole (tsDCH) states in the molecules CO2, N2O and N-2. These experiments are described in detail and the results are compared with simulations of the photoelectron spectra. The double core-hole states, and in particular the tsDCH states, have been predicted to be highly sensitive to the chemical environment. The theory behind this chemical sensitivity is validated by the experiments. Furthermore, our simulations of the relative integrated intensities of the peaks associated with the nonlinear processes show that this type of simulation, in combination with experimental data, provides a useful tool for estimating the duration of ultra-short x-ray pulses.
|
|
| 19. |
- Liu, Ching-Ti, et al.
(författare)
-
Assessment of gene-by-sex interaction effect on bone mineral density
- 2012
-
Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 27:10, s. 2051-2064
-
Tidskriftsartikel (refereegranskat)abstract
- 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?
|
|
| 20. |
- Sahlén, Martin, et al.
(författare)
-
Experimental Verification of the Chemical Sensitivity of Two-Site Double Core-Hole States Formed by an X-Ray Free-Electron Laser
- 2012
-
Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 108:15, s. 153003-
-
Tidskriftsartikel (refereegranskat)abstract
- We have performed x-ray two-photon photoelectron spectroscopy using the Linac Coherent Light Source x-ray free-electron laser in order to study double core-hole (DCH) states of CO2, N2O, and N-2. The experiment verifies the theory behind the chemical sensitivity of two-site DCH states by comparing a set of small molecules with respect to the energy shift of the two-site DCH state and by extracting the relevant parameters from this shift.
|
|
| 21. |
- Saleacuten, P., et al.
(författare)
-
X-ray FEL-induced Double Core-Hole Formation in Polyatomic Molecules
- 2012
-
Ingår i: Journal of Physics, Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 388:2, s. 022083-
-
Tidskriftsartikel (refereegranskat)abstract
- We use extremely intense, ultrashort soft X-Ray pulses generated by the LCLS X-Ray Free Electron Laser to investigate the production of molecular double core-hole states by sequential two-photon X-Ray absorption. The effect of critical LCLS parameters such as the number of photons per pulse, the pulse duration, and the focal spot size on the photoelectron and Auger spectra is modeled in detail and the results of these simulations are used as an aid in the interpretation of the experimental spectra obtained. The emphasis is on double core-hole formation in small polyatomic molecules such as CO2.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
