scholarly journals Genetic contributions to bipolar disorder: current status and future directions

2021 ◽  
pp. 1-12
Author(s):  
Kevin S. O'Connell ◽  
Brandon J. Coombes
Keyword(s):  
Bipolar Disorder ◽  
Large Population ◽  
Population Based ◽  
Therapeutic Interventions ◽  
Current Status ◽  
Genetic Risk Prediction ◽  
Genetic Overlap ◽  
Causal Variants ◽  
Genetic Contributions

Abstract Bipolar disorder (BD) is a highly heritable mental disorder and is estimated to affect about 50 million people worldwide. Our understanding of the genetic etiology of BD has greatly increased in recent years with advances in technology and methodology as well as the adoption of international consortiums and large population-based biobanks. It is clear that BD is also highly heterogeneous and polygenic and shows substantial genetic overlap with other psychiatric disorders. Genetic studies of BD suggest that the number of associated loci is expected to substantially increase in larger future studies and with it, improved genetic prediction of the disorder. Still, a number of challenges remain to fully characterize the genetic architecture of BD. First among these is the need to incorporate ancestrally-diverse samples to move research away from a Eurocentric bias that has the potential to exacerbate health disparities already seen in BD. Furthermore, incorporation of population biobanks, registry data, and electronic health records will be required to increase the sample size necessary for continued genetic discovery, while increased deep phenotyping is necessary to elucidate subtypes within BD. Lastly, the role of rare variation in BD remains to be determined. Meeting these challenges will enable improved identification of causal variants for the disorder and also allow for equitable future clinical applications of both genetic risk prediction and therapeutic interventions.

scholarly journals Molecular and Immune Biomarkers for Cutaneous Melanoma: Current Status and Future Prospects

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3456 ◽  
Author(s):  
Lorenzo Pilla ◽  
Andrea Alberti ◽  
Pierluigi Di Mauro ◽  
Maria Gemelli ◽  
Viola Cogliati ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Predictive Biomarkers ◽  
Therapeutic Interventions ◽  
Current Status ◽  
Immune Biomarkers ◽  
Clinical Responses ◽  
Melanoma Patients ◽  
Immunological Assays ◽  
The Relationship

Advances in the genomic, molecular and immunological make-up of melanoma allowed the development of novel targeted therapy and of immunotherapy, leading to changes in the paradigm of therapeutic interventions and improvement of patients’ overall survival. Nevertheless, the mechanisms regulating either the responsiveness or the resistance of melanoma patients to therapies are still mostly unknown. The development of either the combinations or of the sequential treatment of different agents has been investigated but without a strongly molecularly motivated rationale. The need for robust biomarkers to predict patients’ responsiveness to defined therapies and for their stratification is still unmet. Progress in immunological assays and genomic techniques as long as improvement in designing and performing studies monitoring the expression of these markers along with the evolution of the disease allowed to identify candidate biomarkers. However, none of them achieved a definitive role in predicting patients’ clinical outcomes. Along this line, the cross-talk of melanoma cells with tumor microenvironment plays an important role in the evolution of the disease and needs to be considered in light of the role of predictive biomarkers. The overview of the relationship between the molecular basis of melanoma and targeted therapies is provided in this review, highlighting the benefit for clinical responses and the limitations. Moreover, the role of different candidate biomarkers is described together with the technical approaches for their identification. The provided evidence shows that progress has been achieved in understanding the molecular basis of melanoma and in designing advanced therapeutic strategies. Nevertheless, the molecular determinants of melanoma and their role as biomarkers predicting patients’ responsiveness to therapies warrant further investigation with the vision of developing more effective precision medicine.

scholarly journals Automated Purification of DNA from Large Samples: A Study of Effectiveness and Labor Efficiency

2002 ◽  
Vol 7 (4) ◽  
pp. 38-42 ◽  
Author(s):  
Darin P. O'Brien ◽  
Kristen A. Benedict ◽  
Nathaniel W. Morken ◽  
Ellen M. Heath ◽  
Eugene R. Bleecker ◽  
...  
Keyword(s):  
Large Population ◽  
Population Based ◽  
Purification Process ◽  
Large Samples ◽  
Sample Purification ◽  
Nucleic Acid Purification ◽  
Time Savings ◽  
Family Based ◽  
Automated Instrument ◽  
Genetic Contributions

Investigations into the underlying genetic contributions to human disease are transitioning from small family-based traditional linkage analyses to large population-based studies designed to identify genetic factors in more complex and common diseases that have the greatest impact on human health. These types of studies have driven the need for larger numbers of samples for analysis and more efficient and effective methods for DNA purification, especially for large samples that provide sufficient quantities of DNA for extensive analysis. The Autopure LS™ Nucleic Acid Purification Instrument, by Gentra Systems, Inc., a platform capable of high-throughput sample purification from large samples, was developed to meet the demands of these large studies. This article presents data demonstrating the equivalency of DNA purified using the Autopure LS automated instrument and the manual method based on the same purification process. In addition, we present data demonstrating the in-lab time savings realized by automating the purification process.

scholarly journals The Cerebral Palsy Research Registry

2011 ◽  
Vol 26 (12) ◽  
pp. 1534-1541 ◽  
Author(s):  
Donna S. Hurley ◽  
Theresa Sukal-Moulton ◽  
Michael E. Msall ◽  
Deborah Gaebler-Spira ◽  
Kristin J. Krosschell ◽  
...  
Keyword(s):  
United States ◽  
Cerebral Palsy ◽  
Life Span ◽  
Social Systems ◽  
Large Population ◽  
The United States ◽  
Population Based ◽  
Current Status ◽  
Motor Disability ◽  
Prospective Longitudinal

Cerebral palsy is the most common neurodevelopmental motor disability in children. The condition requires medical, educational, social, and rehabilitative resources throughout the life span. Several countries have developed population-based registries that serve the purpose of prospective longitudinal collection of etiologic, demographic, and functional severity. The United States has not created a comprehensive program to develop such a registry. Barriers have been large population size, poor interinstitution collaboration, and decentralized medical and social systems. The Cerebral Palsy Research Registry was created to fill the gap between population and clinical-based cerebral palsy registries and promote research in the field. This is accomplished by connecting persons with cerebral palsy, as well as their families, to a network of regional researchers. This article describes the development of an expandable cerebral palsy research registry, its current status, and the potential it has to affect families and persons with cerebral palsy in the United States and abroad.

scholarly journals Development and Representativeness of a Large Population-Based Cohort of Native Californian Twins

Twin Research ◽  
2001 ◽  
Vol 4 (4) ◽  
pp. 242-250 ◽  
Author(s):  
Myles G. Cockburn ◽  
Ann S. Hamilton ◽  
John Zadnick ◽  
Wendy Cozen ◽  
Thomas M. Mack
Keyword(s):  
Response Rate ◽  
Large Population ◽  
Population Based ◽  
Multiple Births ◽  
Motor Vehicles ◽  
California Department ◽  
Birth Records ◽  
Residential Distribution ◽  
Near Future

AbstractWe have established a large cohort of twins to facilitate studies of the role of genetics and environment in the development of disease. The cohort has been derived from all multiple births occurring in California between 1908–82 (256,616 in total). We report here on our efforts to contact these twins and their completion of a detailed 16 page risk factor questionnaire. Addresses of the individuals were obtained by linking the birth records with the California Department of Motor Vehicles (DMV) roster of licensees. To date this has been completed for twins born between 1908 and 1972 (200,589 individuals). The linkage has revealed 112,468 matches and, because of less complete DMV records in some years, was less successful in older females than in younger females and all males. Over 41,000 twins have participated by completing the questionnaire. Based on estimates of numbers of individuals receiving a questionnaire, we estimate our crude response rate to be between 42.2% and 49.6%, highest among females in their 40s (62.8%). We describe the representativeness of the twins in the original birth cohort, those identified by the linkage, and those completing the questionnaire. Compared to the 1990 resident population of California-born resident singletons, the respondents were of similar age, sex, race and residential distribution (for although we were able to locate fewer older females, they had a higher response rate), but were less likely to have been educated for more than 12 years. We provide a brief synopsis of studies nested within this cohort. We also elucidate our plans for expanding the cohort in the near future.

Low levels of tissue factor pathway inhibitor (TFPI) increase the risk of venous thrombosis

Blood ◽  
2003 ◽  
Vol 101 (11) ◽  
pp. 4387-4392 ◽  
Author(s):  
Anders Dahm ◽  
Astrid van Hylckama Vlieg ◽  
Bjorn Bendz ◽  
Frits Rosendaal ◽  
Rogier M. Bertina ◽  
...  
Keyword(s):  
Risk Factor ◽  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Large Population ◽  
Population Based ◽  
Vein Thrombosis ◽  
Tissue Factor Pathway ◽  
Low Levels ◽  
Free Antigen

Abstract There is now strong experimental evidence that tissue factor pathway inhibitor (TFPI) is a critical inhibitor to modulate tissue factor–induced coagulation, but the role of TFPI as a risk factor for thrombosis is yet to be to be determined. This study investigated the role of low TFPI levels for the development of deep-vein thrombosis (DVT). We determined TFPI activity and TFPI-free and total antigen levels in the subjects enrolled in the Leiden Thrombophilia Study, which is a large population-based case-control study of 474 patients and 474 controls. The odds ratio (OR) for DVT in subjects who had TFPI-free antigen levels below the 10th percentile, as compared with those who had TFPI-free antigen levels above this cutoff, was 1.7 (95% confidence interval [CI], 1.1-2.6). The ORs for low TFPI activity and low total antigen were also mildly increased. When the 5th percentile was used as a cutoff, the ORs were 2.1 (95% CI, 1.1-4.1) for both TFPI-free antigen and TFPI total antigen. Exogenous female hormones had a profound lowering effect on TFPI levels, with lower levels in oral contraceptive users than in premenopausal nonusers, who had lower levels than men and postmenopausal women. These results indicate that low levels of TFPI, especially low TFPI-free and total antigen in plasma, constitute a risk factor for DVT.

scholarly journals Largely varying patterns and trends of primary cancer-directed resection for gastric carcinoma with synchronous distant metastasis in Europe and the US: a population-based study calling for further standardization of care

2021 ◽  
Vol 13 ◽  
pp. 175883592110278
Author(s):  
Lei Huang ◽  
Lina Jansen ◽  
Rob H.A. Verhoeven ◽  
Jelle P. Ruurda ◽  
Liesbet Van Eycken ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Distant Metastasis ◽  
Associated Factors ◽  
Large Population ◽  
Population Based ◽  
Primary Cancer ◽  
Association Patterns ◽  
Adjacent Structures ◽  
The Us

Aims: The role of resection remains debated in cases of metastatic gastric carcinoma (mGC). Some mGCs are technically resectable. At the population level, the real-world application of resection for mGC remains largely unclear in most Western countries. This large, population-based international investigation aimed to reveal the resection patterns and trends for mGC and the treatment-associated factors in Europe and the US. Methods: Data on cases with microscopically-confirmed primary invasive stomach carcinoma with distant metastasis were obtained from the nationwide cancer registries of the Netherlands, Belgium, Norway, Sweden, Estonia, and Slovenia and the US Surveillance, Epidemiology, and End Results-18 database. We calculated age-standardized rates of primary cancer-directed resection and assessed resection trends using linear regression. We investigated associations of treatment with patient and cancer factors using multivariable-adjusted log-binomial regression. Results: Among 133,321 patients with gastric cancer, overall, 40,215 cases with mGC diagnosed between 2003–2017 were investigated. Age-standardized resection rates significantly declined over time in the US, Belgium, Sweden, and Norway (by 5–14%). Resection rates greatly differed from 5% to 16% in 2013–2014. Cases with older ages, cardia tumors, or tumors involving adjacent structures were significantly less often operated across most countries. Sex was not significantly associated with resection. Across countries the association patterns and strengths differed largely. With multivariable adjustment, resection rates decreased significantly in all countries except Slovenia and Estonia (prevalence ratio per year = 0.90–0.98), and the decreasing trends were consistently observed in various stratifications by age and location. Conclusion: In Europe and the US, resection patterns and trends largely varied across countries for mGCs, which were mostly less often resected in the early 21st century. Various resection-associated factors were shown, with greatly varying association patterns and strengths. Our report could aid to identify discrepancies in clinical practice and highlight the great need for further clarifying the role of resection in mGCs to enhance standardization of care.

scholarly journals THE ROLE OF OCULAR BLOOD FLOW IN THE PATHOGENESIS OF GLAUCOMA

2019 ◽  
Vol 19 (1) ◽  
pp. 51-54
Author(s):  
Yulia Primitasari ◽  
Evelyn Komaratih
Keyword(s):  
Blood Flow ◽  
Large Population ◽  
Visual Fields ◽  
Population Based ◽  
Ocular Blood Flow ◽  
Vascular Risk ◽  
Vascular Dysregulation ◽  
Primary Vascular Dysregulation ◽  
Flicker Stimulation

 Abstract. Glaucoma is currently the second leading cause of blindness worldwide and the prevalence is expected to increase. Despite lowering of IOP, vascular risk factors, genetics, and other systemic conditions could progress the glaucoma damage. Ocular blood flow has emerged as an increasingly prevalent glaucoma risk factor in large population-based trials. Abnormal  perfusion  and  the  subsequent  ischemia  of  the ONH  play  a  major  role  in  the  glaucomatous  damage. Ocular Blood flow is unstable if IOP fluctuates on a high enough or blood pressure on a low enough level to exceed temporarily the autoregulation capacity. IOP fluctuation is also related to both an increase in scotomas and an increase in diffuse visual fields damage.  OBF is unstable if autoregulation itself is disturbed. In  glaucoma  the  response  of  retinal  and  optic nerve head  blood flow to flicker  stimulation  is  reduced.  Primary  vascular  dysregulation appears  to  be  associated  with  abnormal  retinal  neurovascular  coupling,  because  vasospastic  subjects  show  a reduced  response  to  flicker  stimulation.Keywords: ocular blood flow, glaucoma

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