| 1. |
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| 2. |
- Medina-Gomez, C., et al.
(författare)
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Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects
- 2018
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 102:1, s. 88-102
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Tidskriftsartikel (refereegranskat)abstract
- 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. © 2017 American Society of Human Genetics
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| 3. |
- Betoule, M., et al.
(författare)
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Improved cosmological constraints from a joint analysis of the SDSS-II and SNLS supernova samples
- 2014
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 568, s. A22-
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Tidskriftsartikel (refereegranskat)abstract
- Aims. We present cosmological constraints from a joint analysis of type la supernova (SN Ia) observations obtained by the SDSS-II and SNLS collaborations. The dataset includes several low-redshift samples (z < 0.1), all three seasons from the SDSS-11 (0.05 < z < 0.4), and three years from SNLS (0.2 < z < 1), and it totals 740 spectroscopically confirmed type la supernovae with high quality light curves. Methods. We followed the methods and assumptions of the SNLS three-year data analysis except for the following important improvements: I) the addition of the full SDSS-II spectroscopically-confirmed SN la sample in both the training of the SALT2 light-curve model and in the Hubble diagram analysis (374 SNe); 2) intercalibration of the SNLS and SDSS surveys and reduced systematic uncertainties in the photometric calibration, performed blindly with respect to the cosmology analysis; and 3) a thorough investigation of systematic errors associated with the SALT2 modeling of SN la light curves. Results. We produce recalibrated SN la light curves and associated distances for the SDSS-II and SNLS samples. The large SOSS-II sample provides an effective, independent, low -z anchor for the Hubble diagram and reduces the systematic error from calibration systematics in the low -z SN sample. For a flat ACDM cosmology, we find Omega(m), = 0.295 0.034 (stat+sys), a value consistent with the most recent cosmic microwave background (CMB) measurement from the Planck and WMAP experiments. Our result is 1.8 sigma (stat+sys) different than the previously published result of SNLS three-year data. The change is due primarily to improvements in the SNLS photometric calibration. When combined with CMB constraints, we measure a constant dark energy equation of state parameter omega = -1.018 +/- 0,057 (sral+sys) for a fiat universe. Adding baryon acoustic oscillation distance measurements gives similar constraints: omega = 59 -1.027 0.055. Our supernova measurements provide the most stringent constraints to date on the nature of dark energy.
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| 4. |
- Laguzzi, F., et al.
(författare)
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Role of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease : Pooled De Novo Results From 15 Observational Studies
- 2024
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 149:4, s. 305-316
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium.METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction.RESULTS: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; P=0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions.CONCLUSIONS: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD.
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| 5. |
- Ng, M Y M, et al.
(författare)
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Meta-analysis of 32 genome-wide linkage studies of schizophrenia
- 2009
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 14:8, s. 774-785
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Tidskriftsartikel (refereegranskat)abstract
- A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P(SR)) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies.
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| 6. |
- Oskarsdottir, Solveig, 1953, et al.
(författare)
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Updated clinical practice recommendations for managing children with 22q11.2 deletion syndrome
- 2023
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Ingår i: Genetics in Medicine. - : Elsevier BV. - 1098-3600 .- 1530-0366. ; 25:3
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Tidskriftsartikel (refereegranskat)abstract
- This review aimed to update the clinical practice guidelines for managing children and adolescents with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society, the international scientific organization studying chromosome 22q11.2 differences and related conditions, recruited expert clinicians worldwide to revise the original 2011 pediatric clinical practice guidelines in a stepwise process: (1) a systematic literature search (1992-2021), (2) study selection and data extraction by clinical experts from 9 different countries, covering 24 subspecialties, and (3) creation of a draft consensus document based on the literature and expert opinion, which was further shaped by survey results from family support organizations regarding perceived needs. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text reviews, including 1545 meeting criteria for potential relevance to clinical care of children and adolescents. Informed by the available literature, recommendations were formulated. Given evidence base limitations, multidisciplinary recommendations represent consensus statements of good practice for this evolving field. These recommendations provide contemporary guidance for evaluation, surveillance, and management of the many 22q11.2DSassociated physical, cognitive, behavioral, and psychiatric morbidities while addressing important genetic counseling and psychosocial issues.& COPY; 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.
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| 7. |
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| 8. |
- Boot, E., et al.
(författare)
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Updated clinical practice recommendations for managing adults with 22q11.2 deletion syndrome
- 2023
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Ingår i: Genetics in Medicine. - : Elsevier BV. - 1098-3600 .- 1530-0366. ; 25:3
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Tidskriftsartikel (refereegranskat)abstract
- This review aimed to update the clinical practice guidelines for managing adults with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society recruited expert clinicians worldwide to revise the original clinical practice guidelines for adults in a stepwise process according to best practices: (1) a systematic literature search (1992-2021), (2) study selection and synthesis by clinical experts from 8 countries, covering 24 subspecialties, and (3) formulation of consensus recommendations based on the literature and further shaped by patient advocate survey results. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text review, with 2318 meeting inclusion criteria (clinical care relevance to 22q11.2DS) including 894 with potential relevance to adults. The evidence base remains limited. Thus multidisciplinary recommendations represent statements of current best practice for this evolving field, informed by the available literature. These recommendations provide guidance for the recognition, evaluation, surveillance, and management of the many emerging and chronic 22q11.2DS-associated multisystem morbidities relevant to adults. The recommendations also address key genetic counseling and psychosocial considerations for the increasing numbers of adults with this complex condition.& COPY; 2023 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 9. |
- Evans, D. L., et al.
(författare)
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Sustainable futures over the next decade are rooted in soil science
- 2022
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Ingår i: European Journal of Soil Science. - : Wiley. - 1351-0754 .- 1365-2389. ; 73:1
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Tidskriftsartikel (refereegranskat)abstract
- The importance of soils to society has gained increasing recognition over the past decade, with the potential to contribute to most of the United Nations’ Sustainable Development Goals (SDGs). With unprecedented and growing demands for food, water and energy, there is an urgent need for a global effort to address the challenges of climate change and land degradation, whilst protecting soil as a natural resource. In this paper, we identify the contribution of soil science over the past decade to addressing gaps in our knowledge regarding major environmental challenges: climate change, food security, water security, urban development, and ecosystem functioning and biodiversity. Continuing to address knowledge gaps in soil science is essential for the achievement of the SDGs. However, with limited time and budget, it is also pertinent to identify effective methods of working that ensure the research carried out leads to real-world impact. Here, we suggest three strategies for the next decade of soil science, comprising a greater implementation of research into policy, interdisciplinary partnerships to evaluate function trade-offs and synergies between soils and other environmental domains, and integrating monitoring and modelling methods to ensure soil-based policies can withstand the uncertainties of the future. Highlights: We highlight the contributions of soil science to five major environmental challenges since 2010. Researchers have contributed to recommendation reports, but work is rarely translated into policy. Interdisciplinary work should assess trade-offs and synergies between soils and other domains. Integrating monitoring and modelling is key for robust and sustainable soils-based policymaking.
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| 10. |
- Morris, John A, et al.
(författare)
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An atlas of genetic influences on osteoporosis in humans and mice.
- 2019
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 51, s. 258-266
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis is a common aging-related disease diagnosed primarily using bone mineral density (BMD). We assessed genetic determinants of BMD as estimated by heel quantitative ultrasound in 426,824 individuals, identifying 518 genome-wide significant loci (301 novel), explaining 20% of its variance. We identified 13 bone fracture loci, all associated with estimated BMD (eBMD), in ~1.2 million individuals. We then identified target genes enriched for genes known to influence bone density and strength (maximum odds ratio (OR)=58, P=1 × 10-75) from cell-specific features, including chromatin conformation and accessible chromatin sites. We next performed rapid-throughput skeletal phenotyping of 126 knockout mice with disruptions in predicted target genes and found an increased abnormal skeletal phenotype frequency compared to 526 unselected lines (P<0.0001). In-depth analysis of one gene, DAAM2, showed a disproportionate decrease in bone strength relative to mineralization. This genetic atlas provides evidence linking associated SNPs to causal genes, offers new insight into osteoporosis pathophysiology, and highlights opportunities for drug development.
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| 11. |
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| 12. |
- Stahel, P, et al.
(författare)
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Evaluation of the Genetic Association Between Adult Obesity and Neuropsychiatric Disease
- 2019
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 68:12, s. 2235-2246
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Tidskriftsartikel (refereegranskat)abstract
- Extreme obesity (EO) (BMI >50 kg/m2) is frequently associated with neuropsychiatric disease (NPD). As both EO and NPD are heritable central nervous system disorders, we assessed the prevalence of protein-truncating variants (PTVs) and copy number variants (CNVs) in genes/regions previously implicated in NPD in adults with EO (n = 149) referred for weight loss/bariatric surgery. We also assessed the prevalence of CNVs in patients referred to University College London Hospital (UCLH) with EO (n = 218) and obesity (O) (BMI 35–50 kg/m2; n = 374) and a Swedish cohort of participants from the community with predominantly O (n = 161). The prevalence of variants was compared with control subjects in the Exome Aggregation Consortium/Genome Aggregation Database. In the discovery cohort (high NPD prevalence: 77%), the cumulative PTV/CNV allele frequency (AF) was 7.7% vs. 2.6% in control subjects (odds ratio [OR] 3.1 [95% CI 2–4.1]; P < 0.0001). In the UCLH EO cohort (intermediate NPD prevalence: 47%), CNV AF (1.8% vs. 0.9% in control subjects; OR 1.95 [95% CI 0.96–3.93]; P = 0.06) was lower than the discovery cohort. CNV AF was not increased in the UCLH O cohort (0.8%). No CNVs were identified in the Swedish cohort with no NPD. These findings suggest that PTV/CNVs, in genes/regions previously associated with NPD, may contribute to NPD in patients with EO.
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| 13. |
- Blagowidow, N., et al.
(författare)
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Prenatal Screening and Diagnostic Considerations for 22q11.2 Microdeletions
- 2023
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Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Diagnosis of a chromosome 22q11.2 microdeletion and its associated deletion syndrome (22q11.2DS) is optimally made early. We reviewed the available literature to provide contemporary guidance and recommendations related to the prenatal period. Indications for prenatal diagnostic testing include a parent or child with the 22q11.2 microdeletion or suggestive prenatal screening results. Definitive diagnosis by genetic testing of chorionic villi or amniocytes using a chromosomal microarray will detect clinically relevant microdeletions. Screening options include noninvasive prenatal screening (NIPS) and imaging. The potential benefits and limitations of each screening method should be clearly conveyed. NIPS, a genetic option available from 10 weeks gestational age, has a 70-83% detection rate and a 40-50% PPV for most associated 22q11.2 microdeletions. Prenatal imaging, usually by ultrasound, can detect several physical features associated with 22q11.2DS. Findings vary, related to detection methods, gestational age, and relative specificity. Conotruncal cardiac anomalies are more strongly associated than skeletal, urinary tract, or other congenital anomalies such as thymic hypoplasia or cavum septi pellucidi dilatation. Among others, intrauterine growth restriction and polyhydramnios are additional associated, prenatally detectable signs. Preconception genetic counselling should be offered to males and females with 22q11.2DS, as there is a 50% risk of transmission in each pregnancy. A previous history of a de novo 22q11.2 microdeletion conveys a low risk of recurrence. Prenatal genetic counselling includes an offer of screening or diagnostic testing and discussion of results. The goal is to facilitate optimal perinatal care.
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| 14. |
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| 15. |
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| 16. |
- Lai, Heidi T. M., et al.
(författare)
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Trans Fatty Acid Biomarkers and Incident Type 2 Diabetes : Pooled Analysis of 12 Prospective Cohort Studies in the Fatty Acids and Outcomes Research Consortium (FORCE)
- 2022
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 45:4, s. 854-863
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Trans fatty acids (TFAs) have harmful biologic effects that could increase the risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFA biomarkers and T2D by conducting an individual participant-level pooled analysis.RESEARCH DESIGN AND METHODS: We included data from an international consortium of 12 prospective cohorts and nested case-control studies from six nations. TFA biomarkers were measured in blood collected between 1990 and 2008 from 25,126 participants aged >= 18 years without prevalent diabetes. Each cohort conducted de novo harmonized analyses using a prespecified protocol, and findings were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by prespecified between-study and within-study characteristics.RESULTS: During a mean follow-up of 13.5 years, 2,843 cases of incident T2D were identified. In multivariable-adjusted pooled analyses, no significant associations with T2D were identified for trans/trans-18:2, relative risk (RR) 1.09 (95% CI 0.94-1.25); cis/trans-18:2, 0.89 (0.73-1.07); and trans/cis-18:2, 0.87 (0.73-1.03). Trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated with T2D (RR 0.81 [95% CI 0.67-0.99], 0.86 [0.75-0.99], and 0.84 [0.74-0.96], respectively). Findings were not significantly different according to prespecified sources of potential heterogeneity (each P >= 0.1).CONCLUSIONS: Circulating individual trans-18:2 TFA biomarkers were not associated with risk of T2D, while trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated. Findings may reflect the influence of mixed TFA sources (industrial vs. natural ruminant), a general decline in TFA exposure due to policy changes during this period, or the relatively limited range of TFA levels.
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| 17. |
- Lampeitl, H., et al.
(författare)
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First-year Sloan Digital Sky Survey-II supernova results : consistency and constraints with other intermediate-redshift data sets
- 2010
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 401:4, s. 2331-2342
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Tidskriftsartikel (refereegranskat)abstract
- We present an analysis of the luminosity distances of Type Ia Supernovae (SNe) from the Sloan Digital Sky Survey-II (SDSS-II) SN Survey in conjunction with other intermediate-redshift (z < 0.4) cosmological measurements including redshift-space distortions from the Two-Degree Field Galaxy Redshift Survey (2dFGRS), the integrated Sachs–Wolfe (ISW) effect seen by the SDSS and the latest baryon acoustic oscillation (BAO) distance scale from both the SDSS and 2dFGRS. We have analysed the SDSS-II SN data alone using a variety of ‘model-independent’ methods and find evidence for an accelerating Universe at a >97 per cent level from this single data set. We find good agreement between the SN and BAO distance measurements, both consistent with a Λ-dominated cold dark matter cosmology, as demonstrated through an analysis of the distance duality relationship between the luminosity (dL) and angular diameter (dA) distance measures. We then use these data to estimate w within this restricted redshift range (z < 0.4). Our most stringent result comes from the combination of all our intermediate-redshift data (SDSS-II SNe, BAO, ISW and redshift-space distortions), giving w=−0.81+0.16−0.18 (stat) ± 0.15 (sys) and ΩM= 0.22+0.09−0.08 assuming a flat universe. This value of w and associated errors only change slightly if curvature is allowed to vary, consistent with constraints from the cosmic microwave background. We also consider more limited combinations of the geometrical (SN, BAO) and dynamical (ISW, redshift-space distortions) probes.
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| 18. |
- Paluch, Amanda E., et al.
(författare)
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Daily steps and all-cause mortality : a meta-analysis of 15 international cohorts
- 2022
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Ingår i: The Lancet Public Health. - : Elsevier. - 2468-2667. ; 7:3, s. e219-e228
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although 10 000 steps per day is widely promoted to have health benefits, there is little evidence to support this recommendation. We aimed to determine the association between number of steps per day and stepping rate with all-cause mortality.METHODS: In this meta-analysis, we identified studies investigating the effect of daily step count on all-cause mortality in adults (aged ≥18 years), via a previously published systematic review and expert knowledge of the field. We asked participating study investigators to process their participant-level data following a standardised protocol. The primary outcome was all-cause mortality collected from death certificates and country registries. We analysed the dose-response association of steps per day and stepping rate with all-cause mortality. We did Cox proportional hazards regression analyses using study-specific quartiles of steps per day and calculated hazard ratios (HRs) with inverse-variance weighted random effects models.FINDINGS: We identified 15 studies, of which seven were published and eight were unpublished, with study start dates between 1999 and 2018. The total sample included 47 471 adults, among whom there were 3013 deaths (10·1 per 1000 participant-years) over a median follow-up of 7·1 years ([IQR 4·3-9·9]; total sum of follow-up across studies was 297 837 person-years). Quartile median steps per day were 3553 for quartile 1, 5801 for quartile 2, 7842 for quartile 3, and 10 901 for quartile 4. Compared with the lowest quartile, the adjusted HR for all-cause mortality was 0·60 (95% CI 0·51-0·71) for quartile 2, 0·55 (0·49-0·62) for quartile 3, and 0·47 (0·39-0·57) for quartile 4. Restricted cubic splines showed progressively decreasing risk of mortality among adults aged 60 years and older with increasing number of steps per day until 6000-8000 steps per day and among adults younger than 60 years until 8000-10 000 steps per day. Adjusting for number of steps per day, comparing quartile 1 with quartile 4, the association between higher stepping rates and mortality was attenuated but remained significant for a peak of 30 min (HR 0·67 [95% CI 0·56-0·83]) and a peak of 60 min (0·67 [0·50-0·90]), but not significant for time (min per day) spent walking at 40 steps per min or faster (1·12 [0·96-1·32]) and 100 steps per min or faster (0·86 [0·58-1·28]).INTERPRETATION: Taking more steps per day was associated with a progressively lower risk of all-cause mortality, up to a level that varied by age. The findings from this meta-analysis can be used to inform step guidelines for public health promotion of physical activity.FUNDING: US Centers for Disease Control and Prevention.
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| 19. |
- Imamura, Fumiaki, et al.
(författare)
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Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes : A pooled analysis of prospective cohort studies
- 2018
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 15:10
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Tidskriftsartikel (refereegranskat)abstract
- Background We aimed to investigate prospective associations of circulating or adipose tissue odd-chain fatty acids 15: 0 and 17: 0 and trans-palmitoleic acid, t16:1n-7, as potential biomarkers of dairy fat intake, with incident type 2 diabetes (T2D). Methods and findings Sixteen prospective cohorts from 12 countries (7 from the United States, 7 from Europe, 1 from Australia, 1 from Taiwan) performed new harmonised individual-level analysis for the prospective associations according to a standardised plan. In total, 63,682 participants with a broad range of baseline ages and BMIs and 15,180 incident cases of T2D over the average of 9 years of follow-up were evaluated. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Prespecified interactions by age, sex, BMI, and race/ethnicity were explored in each cohort and were meta-analysed. Potential heterogeneity by cohort-specific characteristics (regions, lipid compartments used for fatty acid assays) was assessed with metaregression. After adjustment for potential confounders, including measures of adiposity (BMI, waist circumference) and lipogenesis (levels of palmitate, tri-glycerides), higher levels of 15:0, 17:0, and t16:1n-7 were associated with lower incidence of T2D. In the most adjusted model, the hazard ratio (95% CI) for incident T2D per cohort-specific 10th to 90th percentile range of 15:0 was 0.80 (0.73-0.87); of 17:0, 0.65 (0.59-0.72); of t16:1n7, 0.82 (0.70-0.96); and of their sum, 0.71 (0.63-0.79). In exploratory analyses, similar associations for 15:0, 17:0, and the sum of all three fatty acids were present in both genders but stronger in women than in men ((pinteraction) < 0.001). Whereas studying associations with biomarkers has several advantages, as limitations, the biomarkers do not distinguish between different food sources of dairy fat (e.g., cheese, yogurt, milk), and residual confounding by unmeasured or imprecisely measured confounders may exist. Conclusions In a large meta-analysis that pooled the findings from 16 prospective cohort studies, higher levels of 15:0, 17:0, and t16:1n-7 were associated with a lower risk of T2D.
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| 20. |
- Imamura, Fumiaki, et al.
(författare)
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Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes : A pooled analysis of prospective cohort studies
- 2020
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 17:6
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDe novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D).Methods and findingsSeventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970–1973 to 2006–2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3–75.5 years; % women = 20.4%–62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41–1.66; p < 0.001) for 16:0, 1.40 (1.33–1.48; p < 0.001) for 16:1n-7, 1.14 (1.05–1.22; p = 0.001) for 18:0, and 1.16 (1.07–1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%–73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94–1.13). These findings had limitations in potential reverse causation and residual confounding by imprecisely measured or unmeasured factors.ConclusionsConcentrations of fatty acids in the DNL were positively associated with T2D incidence. Our findings support further work to investigate a possible role of DNL and individual fatty acids in the development of T2D.
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| 21. |
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| 22. |
- Sako, Masao, et al.
(författare)
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The Data Release of the Sloan Digital Sky Survey-II Supernova Survey
- 2018
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 130:988
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the data release of the Sloan Digital Sky Survey-II (SDSS-II) Supernova Survey conducted between 2005 and 2007. Light curves, spectra, classifications, and ancillary data are presented for 10,258 variable and transient sources discovered through repeat ugriz imaging of SDSS Stripe 82, a 300 deg(2) area along the celestial equator. This data release is comprised of all transient sources brighter than r similar or equal to 22.5 mag with no history of variability prior to 2004. Dedicated spectroscopic observations were performed on a subset of 889 transients, as well as spectra for thousands of transient host galaxies using the SDSS-III BOSS spectrographs. Photometric classifications are provided for the candidates with good multi-color light curves that were not observed spectroscopically, using host galaxy redshift information when available. From these observations, 4607 transients are either spectroscopically confirmed, or likely to be, supernovae, making this the largest sample of supernova candidates ever compiled. We present a new method for SN host-galaxy identification and derive host-galaxy properties including stellar masses, star formation rates, and the average stellar population ages from our SDSS multi-band photometry. We derive SALT2 distance moduli for a total of 1364 SN. Ia with spectroscopic redshifts as well as photometric redshifts for a further 624 purely photometric SN. Ia candidates. Using the spectroscopically confirmed subset of the three-year SDSS-II SN. Ia sample and assuming a flat.CDM cosmology, we determine Omega(M) = 0.315 +/- 0.093 (statistical error only) and detect a non-zero cosmological constant at 5.7 sigma.
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| 23. |
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| 24. |
- Courseaux, A, et al.
(författare)
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Definition of the minimal MEN 1 candidate area based on a 5-Mb integrated map proximal to 11q13 : The european consortium on men1
- 1996
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 37:3, s. 345-353
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Tidskriftsartikel (refereegranskat)abstract
- Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with a high penetrance characterized by tumors of the parathyroid glands, the endocrine pancreas, and the anterior pituitary. The MEN1 gene, a putative tumor suppressor gene, has been mapped to a 3- to 8-cM region in chromosome 11q13 but it remains elusive as yet. We have combined the efforts and resources from four laboratories to form the European Consortium on MEN1 with the aims of establishing the genetic and the physical maps of 11q13 and of further narrowing the MEN1 region. A 5-Mb integrated map of the region was established by fluorescence in situ hybridization on both metaphase chromosomes and DNA fibers, by hybridization to DNA from somatic cell hybrids containing various parts of human chromosome 11, by long-range restriction mapping, and by characterization of YACs and cosmids. Polymorphic markers were positioned and ordered by physical mapping and genetic linkage in 86 MEN1 families with 452 affected individuals. Two critical recombinants identified in two affected cases placed the MEN1 gene in an approximately 2-Mb region around PYGM, flanked by D11S1883 and D11S449.
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| 25. |
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| 26. |
- Feng, Xiaoshuang, et al.
(författare)
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Lung cancer risk discrimination of prediagnostic proteomics measurements compared with existing prediction tools
- 2023
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 115:9, s. 1050-1059
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test.METHODS: We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models' sensitivity. All tests were 2-sided.RESULTS: The area under the curve for the protein-based risk model in the validation sample was 0.75 (95% confidence interval [CI] = 0.70 to 0.81) compared with 0.64 (95% CI = 0.57 to 0.70) for the PLCOm2012 model (Pdifference = .001). The EarlyCDT-Lung had a sensitivity of 14% (95% CI = 8.2% to 19%) and a specificity of 86% (95% CI = 81% to 92%) for incident lung cancer. At the same specificity of 86%, the sensitivity for the protein-based risk model was estimated at 49% (95% CI = 41% to 57%) and 30% (95% CI = 23% to 37%) for the PLCOm2012 model.CONCLUSION: Circulating proteins showed promise in predicting incident lung cancer and outperformed a standard risk prediction model and the commercialized EarlyCDT-Lung.
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| 27. |
- Formosa, MM, et al.
(författare)
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A Roadmap to Gene Discoveries and Novel Therapies in Monogenic Low and High Bone Mass Disorders
- 2021
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Ingår i: Frontiers in endocrinology. - : Frontiers Media SA. - 1664-2392. ; 12, s. 709711-
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Tidskriftsartikel (refereegranskat)abstract
- Genetic disorders of the skeleton encompass a diverse group of bone diseases differing in clinical characteristics, severity, incidence and molecular etiology. Of particular interest are the monogenic rare bone mass disorders, with the underlying genetic defect contributing to either low or high bone mass phenotype. Extensive, deep phenotyping coupled with high-throughput, cost-effective genotyping is crucial in the characterization and diagnosis of affected individuals. Massive parallel sequencing efforts have been instrumental in the discovery of novel causal genes that merit functional validation using in vitro and ex vivo cell-based techniques, and in vivo models, mainly mice and zebrafish. These translational models also serve as an excellent platform for therapeutic discovery, bridging the gap between basic science research and the clinic. Altogether, genetic studies of monogenic rare bone mass disorders have broadened our knowledge on molecular signaling pathways coordinating bone development and metabolism, disease inheritance patterns, development of new and improved bone biomarkers, and identification of novel drug targets. In this comprehensive review we describe approaches to further enhance the innovative processes taking discoveries from clinic to bench, and then back to clinic in rare bone mass disorders. We highlight the importance of cross laboratory collaboration to perform functional validation in multiple model systems after identification of a novel disease gene. We describe the monogenic forms of rare low and high rare bone mass disorders known to date, provide a roadmap to unravel the genetic determinants of monogenic rare bone mass disorders using proper phenotyping and genotyping methods, and describe different genetic validation approaches paving the way for future treatments.
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| 28. |
- Lewis, Cathryn M, et al.
(författare)
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Genome scan meta-analysis of schizophrenia and bipolar disorder, part II : Schizophrenia
- 2003
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Ingår i: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 73:1, s. 34-48
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.
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| 29. |
- Lurie, DJ, et al.
(författare)
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Questions and controversies in the study of time-varying functional connectivity in resting fMRI
- 2020
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Ingår i: Network neuroscience (Cambridge, Mass.). - : MIT Press - Journals. - 2472-1751. ; 4:1, s. 30-69
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Tidskriftsartikel (refereegranskat)abstract
- The brain is a complex, multiscale dynamical system composed of many interacting regions. Knowledge of the spatiotemporal organization of these interactions is critical for establishing a solid understanding of the brain’s functional architecture and the relationship between neural dynamics and cognition in health and disease. The possibility of studying these dynamics through careful analysis of neuroimaging data has catalyzed substantial interest in methods that estimate time-resolved fluctuations in functional connectivity (often referred to as “dynamic” or time-varying functional connectivity; TVFC). At the same time, debates have emerged regarding the application of TVFC analyses to resting fMRI data, and about the statistical validity, physiological origins, and cognitive and behavioral relevance of resting TVFC. These and other unresolved issues complicate interpretation of resting TVFC findings and limit the insights that can be gained from this promising new research area. This article brings together scientists with a variety of perspectives on resting TVFC to review the current literature in light of these issues. We introduce core concepts, define key terms, summarize controversies and open questions, and present a forward-looking perspective on how resting TVFC analyses can be rigorously and productively applied to investigate a wide range of questions in cognitive and systems neuroscience.
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| 30. |
- Qian, Frank, et al.
(författare)
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n-3 Fatty Acid Biomarkers and Incident Type 2 Diabetes : An Individual Participant-Level Pooling Project of 20 Prospective Cohort Studies
- 2021
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 44:5, s. 1133-1142
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis.RESEARCH DESIGN AND METHODS For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed in each cohort following a pre-specified protocol, and cohort-specific associations were pooled using inverse variance-weighted meta-analysis.RESULTS A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per interquintile range (difference between the 90th and 10th percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% CIs of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89), and 0.81 (0.75, 0.88), respectively (all P < 0.001). ALA was not associated with T2D (HR 0.97 [95% CI 0.92, 1.02]) per interquintile range. Associations were robust across prespecified subgroups as well as in sensitivity analyses.CONCLUSIONS Higher circulating biomarkers of seafood-derived n-3 fatty acids, including EPA, DPA, DHA, and their sum, were associated with lower risk of T2D in a global consortium of prospective studies. The biomarker of plant-derived ALA was not significantly associated with T2D risk.
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| 31. |
- Vogel, Jacob W., et al.
(författare)
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Connectome-based modelling of neurodegenerative diseases: towards precision medicine and mechanistic insight
- 2023
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Ingår i: Nature Reviews Neuroscience. - 1471-003X .- 1471-0048. ; 24:10, s. 620-639
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Tidskriftsartikel (refereegranskat)abstract
- Neurodegenerative diseases are the most common cause of dementia. Although their underlying molecular pathologies have been identified, there is substantial heterogeneity in the patterns of progressive brain alterations across and within these diseases. Recent advances in neuroimaging methods have revealed that pathological proteins accumulate along specific macroscale brain networks, implicating the network architecture of the brain in the system-level pathophysiology of neurodegenerative diseases. However, the extent to which 'network-based neurodegeneration' applies across the wide range of neurodegenerative disorders remains unclear. Here, we discuss the state-of-the-art of neuroimaging-based connectomics for the mapping and prediction of neurodegenerative processes. We review findings supporting brain networks as passive conduits through which pathological proteins spread. As an alternative view, we also discuss complementary work suggesting that network alterations actively modulate the spreading of pathological proteins between connected brain regions. We conclude this Perspective by proposing an integrative framework in which connectome-based models can be advanced along three dimensions of innovation: incorporating parameters that modulate propagation behaviour on the basis of measurable biological features; building patient-tailored models that use individual-level information and allowing model parameters to interact dynamically over time. We discuss promises and pitfalls of these strategies for improving disease insights and moving towards precision medicine. Neurodegenerative diseases show idiosyncratic spatial patterns of progressive protein malformations in the brain. In this Perspective, Vogel et al. discuss the role of inter-regional connectivity in constraining and modulating the spread of pathological proteins and provide a framework for patient-tailored prognostics.
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| 32. |
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| 33. |
- Campbell, Heather, et al.
(författare)
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COSMOLOGY WITH PHOTOMETRICALLY CLASSIFIED TYPE Ia SUPERNOVAE FROM THE SDSS-II SUPERNOVA SURVEY
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 763:2, s. 88-
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Tidskriftsartikel (refereegranskat)abstract
- We present the cosmological analysis of 752 photometrically classified Type Ia Supernovae (SNe Ia) obtained from the full Sloan Digital Sky Survey II (SDSS-II) Supernova (SN) Survey, supplemented with host-galaxy spectroscopy from the SDSS-III Baryon Oscillation Spectroscopic Survey. Our photometric-classification method is based on the SN classification technique of Sako et al., aided by host-galaxy redshifts (0.05 < z < 0.55). SuperNova ANAlysis simulations of our methodology estimate that we have an SN Ia classification efficiency of 70.8%, with only 3.9% contamination from core-collapse (non-Ia) SNe. We demonstrate that this level of contamination has no effect on our cosmological constraints. We quantify and correct for our selection effects (e. g., Malmquist bias) using simulations. When fitting to a flat.CDM cosmological model, we find that our photometric sample alone gives Omega(m) = 0.24(-0.05)(+0.07) (statistical errors only). If we relax the constraint on flatness, then our sample provides competitive joint statistical constraints on Omega(m) and Omega(Lambda), comparable to those derived from the spectroscopically confirmed Three-year Supernova Legacy Survey (SNLS3). Using only our data, the statistics-only result favors an accelerating universe at 99.96% confidence. Assuming a constant wCDM cosmological model, and combining with H-0, cosmic microwave background, and luminous red galaxy data, we obtain w = -0.96(-0.10)(+0.10), Omega(m) = 0.29(-0.02)(+0.02), and Omega(k) = 0.00(-0.02)(+0.03)(statistical errors only), which is competitive with similar spectroscopically confirmed SNe Ia analyses. Overall this comparison is reassuring, considering the lower redshift leverage of the SDSS-II SN sample (z < 0.55) and the lack of spectroscopic confirmation used herein. These results demonstrate the potential of photometrically classified SN Ia samples in improving cosmological constraints.
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| 34. |
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| 35. |
- Kremer, B, et al.
(författare)
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A worldwide study of the Huntington's disease mutation. The sensitivity and specificity of measuring CAG repeats.
- 1994
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 330:20, s. 1401-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Huntington's disease is associated with an expanded sequence of CAG repeats in a gene on chromosome 4p16.3. However, neither the sensitivity of expanded CAG repeats in affected persons of different ethnic origins nor the specificity of such repeats for Huntington's disease as compared with other neuropsychiatric disorders has been determined.METHODS: We studied 1007 patients with diagnosed Huntington's disease from 565 families and 43 national and ethnic groups. In addition, the length of the CAG repeat was determined in 113 control subjects with a family history of Alzheimer's disease (44 patients), schizophrenia (39), major depression (16), senile chorea (5), benign hereditary chorea (5), neuroacanthocytosis (2), and dentatorubropallidoluysian atrophy (2). The number of CAG repeats was also assessed in 1595 control chromosomes, with the size of adjacent polymorphic CCG trinucleotide repeats taken into account.RESULTS: Of 1007 patients with signs and symptoms compatible with a diagnosis of Huntington's disease, 995 had an expanded CAG repeat that included from 36 to 121 repeats (median, 44) (sensitivity, 98.8 percent; 95 percent confidence interval, 97.7 to 99.4 percent). There were no significant differences among national and ethnic groups in the number of repeats. No CAG expansion was found in the 110 control subjects with other neuropsychiatric disorders (specificity, 100 percent; 95 percent confidence interval, 95.2 to 100 percent). In 1581 of the 1595 control chromosomes (99.1 percent), the number of CAG repeats ranged from 10 to 29 (median, 18). In 12 control chromosomes (0.75 percent), intermediate-sized CAG sequences with 30 to 35 repeats were found, and 2 normal chromosomes unexpectedly had expanded CAG sequences, of 39 and 37 repeats.CONCLUSIONS: CAG trinucleotide expansion is the molecular basis of Huntington's disease worldwide and is a highly sensitive and specific marker for inheritance of the disease mutation.
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| 36. |
- Paluch, Amanda E., et al.
(författare)
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Prospective association of daily steps with cardiovascular disease : a harmonized meta-analysis
- 2023
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 147:2, s. 122-131
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Taking fewer than the widely promoted "10 000 steps per day" has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose-response relationship between steps per day and CVD can help inform clinical and public health guidelines.METHODS: Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional hazards regression analyses were completed using study-specific quartiles and hazard ratios (HR) and 95% CI were meta-analyzed with inverse-variance-weighted random effects models.RESULTS: The mean age of participants was 63.2±12.4 years and 52% were women. The mean follow-up was 6.2 years (123 209 person-years), with a total of 1523 CVD events (12.4 per 1000 participant-years) reported. There was a significant difference in the association of steps per day and CVD between older (ie, ≥60 years of age) and younger adults (ie, <60 years of age). For older adults, the HR for quartile 2 was 0.80 (95% CI, 0.69 to 0.93), 0.62 for quartile 3 (95% CI, 0.52 to 0.74), and 0.51 for quartile 4 (95% CI, 0.41 to 0.63) compared with the lowest quartile. For younger adults, the HR for quartile 2 was 0.79 (95% CI, 0.46 to 1.35), 0.90 for quartile 3 (95% CI, 0.64 to 1.25), and 0.95 for quartile 4 (95% CI, 0.61 to 1.48) compared with the lowest quartile. Restricted cubic splines demonstrated a nonlinear association whereby more steps were associated with decreased risk of CVD among older adults.CONCLUSIONS: For older adults, taking more daily steps was associated with a progressively decreased risk of CVD. Monitoring and promoting steps per day is a simple metric for clinician-patient communication and population health to reduce the risk of CVD.
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| 37. |
- Vanden Wymelenberg, A., et al.
(författare)
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Transcript analysis of genes encoding a family 61 endoglucanase and a putative membrane-anchored family 9 glycosyl hydrolase from Phanerochaete chrysosporium
- 2002
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Ingår i: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 68:11, s. 5765-5768
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Tidskriftsartikel (refereegranskat)abstract
- Phanerochaete chrysosporium cellulase genes were cloned and characterized. The cel61A product was structurally similar to fungal endoglucanases of glycoside hydrolase family 61, whereas the cel9A product revealed similarities to Thermobifida fusca Cel9A (E4), an enzyme with both endo- and exocellulase characteristics. The fungal Cel9A is apparently a membrane-bound protein, which is very unusual for microbial cellulases. Transcript levels of both genes were substantially higher in cellulose-grown cultures than in glucose-grown cultures. These results show that P. chrysosporium possesses a wide array of conventional and unconventional cellulase genes.
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