scholarly journals Life Writing in the Era of Genetics: Contemporary Genetic Risk Narratives in Great Britain and America

2021 ◽  
Vol 11 (3) ◽  
pp. 45
Author(s):  
Tingting Zhou
Keyword(s):  
Great Britain ◽  
Genetic Risk ◽  
Risk Group ◽  
High Risk Group ◽  
The Body ◽  
Personal Meaning ◽  
Complex Situation ◽  
Genetic Risks ◽  
Disease Related Genes ◽  
Genetic Science

The development of genetic science brings forth a third group besides the healthy and the ill: the high-risk group who carries certain disease-related genes. In the era of genetics, people try to assess risks with statistical numbers and eliminate risks by Western medical measures. In this context, personal genetic risk narratives (usually in the form of memoirs) emerged in Great Britain and America in the 1990s. The thesis has a close reading of three British and American genetic risk memoirs and wants to find the characteristics and values of the new genre. The memoirs are featured by their vivid description of the narrator’s difficult and complex situation in face of genetic risks. In an era when the body is dominated by statistical numbers, these narratives make personal meaning of impersonal statistics. Genetic risk narratives express a strong belief in genetic technology and Western medical myth. However, the narrative divergence and self-contradiction in the memoirs exposes the limitation of genetic determinism and thus deconstructs the Western medical myth.

scholarly journals Alterations in resting-state activity and functional connectivity in children with 22q11.2 deletion syndrome

2021 ◽  
Author(s):  
Joanne L Doherty ◽  
Adam C Cunningham ◽  
Samuel JRA Chawner ◽  
Hayley M Moss ◽  
Diana C Dima ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Genetic Risk ◽  
Risk Group ◽  
22Q11.2 Deletion Syndrome ◽  
High Risk Group ◽  
Oscillatory Activity ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Band Activity

Background While genetic risk factors for psychiatric and neurodevelopmental disorders have been identified, the neurobiological route from genetic risk to neuropsychiatric outcome remains unclear. 22q11.2 deletion syndrome (22q11.2DS) is a copy number variant (CNV) syndrome associated with high rates of neurodevelopmental and psychiatric disorders including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and schizophrenia. Alterations in neural integration and cortical connectivity have been linked to the spectrum of neuropsychiatric disorders seen in 22q11.2DS and may be a mechanism by which the CNV acts to increase risk. Despite this, few studies have investigated electrophysiological connectivity in this high-risk group. Studying children with 22q11.2DS provides a unique paradigm to identify brain markers of neurodevelopmental impairment and to relate these to underlying biology. Methods Magnetoencephalography (MEG) was used to investigate resting-state cortical oscillatory patterns in 34 children with 22q11.2DS and 25 controls aged 10-17 years old. Oscillatory activity and functional connectivity across six frequency bands were compared between groups. Regression analyses were used to explore the relationships between these measures, IQ and neurodevelopmental symptoms. Results Children with 22q11.2DS had atypical oscillatory activity and functional connectivity across multiple frequency bands (delta, beta and gamma bands). In the 22q11.2DS group, low frequency (alpha band) activity was negatively associated with cognitive ability and positively associated with ASD and ADHD symptoms. Frontal high frequency (gamma band) activity and connectivity were positively associated with ASD and ADHD symptoms, while posterior gamma activity was negatively associated with ASD symptoms. Conclusions These findings highlight that haploinsufficiency at the 22q11.2 locus alters both local and long-range cortical circuitry, which could be a mechanism underlying neurodevelopmental vulnerability in this high risk group.

scholarly journals Development and validation of decision rules models to stratify coronary artery disease, diabetes, and hypertension risk in preventive care: cohort study of returning UK Biobank participants

2021 ◽  
Author(s):  
José Castela Forte ◽  
Pytrik Folkertsma ◽  
Rahul Gannamani ◽  
Sridhar Kumaraswamy ◽  
Sarah Mount ◽  
...  
Keyword(s):  
Lifestyle Intervention ◽  
Genetic Risk ◽  
Risk Group ◽  
Decision Rules ◽  
High Risk Group ◽  
Risk Scores ◽  
Uk Biobank ◽  
Physical Measurements ◽  
The Uk

AbstractBackgroundA wide range of predictive models exist that predict risk of common lifestyle conditions. However, these have not focused on identifying pre-clinical higher risk groups that would benefit from lifestyle interventions and do not include genetic risk scores. In this study, we developed, validated, and compared the performance of three decision rule algorithms including biomarkers, physical measurements and genetic risk scores for incident coronary artery disease (CAD), diabetes (T2D), and hypertension in the general population against commonly used clinical risk scoring tools.Methods and findingsOf all individuals recruited between 2006 and 2010 from the UK Biobank study for whom re-measurement data were available, 60782 were included in the analyses (mean age 56.3 (7.59), 51.2% female). Follow-up data were available until 2016. Three decision rules models with three risk strata were developed and tested for an association with incident disease. Hazard ratios (HR with 95% confidence interval) for incident CAD, T2D, and hypertension were calculated from survival models. Model performance in discriminating between higher risk individuals suitable for lifestyle intervention and individuals at low risk was assessed using the area under the receiver operating characteristic curve (AUROC).From the initial baseline measurement until the follow-up re-measurements, 500 incident CAD cases, 1005 incident T2D cases, and 2379 incident hypertension cases were ascertained. The higher risk group in the decision rules model had a 40-, 40.9-, and 21.6-fold increase in risk of CAD, T2D, and hypertension, respectively (P < 0.001 for all), and the risk increased significantly between the three strata for all three conditions (P < 0.05). Risk stratification based on decision rules identified both a low risk group which would not have benefited from lifestyle intervention (only 1.3% incident disease across all models), as well as a high risk group where 72%, 81.5%, and 74% of those who developed disease within 8 years would have been recommended lifestyle intervention. Based on genetic risk alone, we identified not only a high risk group, but also a group at elevated risk for all health conditions. This study was limited by the restricted number of participants with follow-up data, and the lack of ethnic diversity in the UK Biobank cohort.ConclusionIn this analysis of returning UK Biobank participants, we found that decision rule models comprising blood biomarkers, physical measurements, and polygenic risk scores were superior at identifying individuals likely to benefit from lifestyle intervention for three of the most common lifestyle-related chronic health conditions compared to commonly used clinical risk scores.

Differentiation of adoptees at high versus low genetic risk for schizophrenia by adjusted MMPI indices

2006 ◽  
Vol 21 (4) ◽  
pp. 245-250 ◽  
Author(s):  
Virva Siira ◽  
Karl-Erik Wahlberg ◽  
Jouko Miettunen ◽  
Pekka Tienari ◽  
Kristian Làksy
Keyword(s):  
Genetic Risk ◽  
Minnesota Multiphasic Personality Inventory ◽  
Risk Group ◽  
High Risk Group ◽  
Adoptive Family ◽  
Genetic Vulnerability ◽  
Biological Mothers ◽  
High Genetic Risk ◽  
Schizophrenia Spectrum ◽  
And Control

AbstractThe aim of this study was to find potential signs of genetic vulnerability to schizophrenia. The differences between adoptees at high genetic risk for schizophrenia (their biological mother had a schizophrenia spectrum disorder) and control adoptees of non-schizophrenia spectrum biological mothers were assessed. The comparisons between these groups were based on the Minnesota Multiphasic Personality Inventory (MMPI) test's subscale scores adjusted by gender, age at MMPI assessment, age at placement into the adoptive family and social class. The subjects were a subsamples of a total of 182 tested adoptees and 136 mentally healthy adoptees in the Finnish Adoptive Family Study. The high-risk group was found to be distinguishable from the low-risk group based on deviant scores on the Hostility, Hypomania and Lie scales. These scales may measure genetic vulnerability and also possibly be indicative of psychometric deviance predicting future onset of schizophrenia.

Can Autism be Detected at 18 Months?

1992 ◽  
Vol 161 (6) ◽  
pp. 839-843 ◽  
Author(s):  
Simon Baron-Cohen ◽  
Jane Allen ◽  
Christopher Gillberg
Keyword(s):  
High Risk ◽  
Genetic Risk ◽  
Risk Group ◽  
Pretend Play ◽  
Social Play ◽  
High Risk Group ◽  
High Genetic Risk ◽  
Health Visitors ◽  
New Instrument

Autism is currently detected only at about three years of age. This study aimed to establish if detection of autism was possible at 18 months of age. We screened 41 18–month-old toddlers who were at high genetic risk for developing autism, and 50 randomly selected 18–month-olds, using a new instrument, the CHAT, administered by GPs or health visitors. More than 80% of the randomly selected 18–month-old toddlers passed on all items, and none failed on more than one of pretend play, protodeclarative pointing, joint-attention, social interest, and social play. Four children in the high-risk group failed on two or more of these five key types of behaviour. At follow-up at 30 months of age, the 87 children who had passed four or more of these key types of behaviour at 18 months of age had continued to develop normally. The four toddlers who had failed on two or more of these key types of behaviour at 18 months received a diagnosis of autism by 30 months.

scholarly journals Clinical Relevance of Somatic Mutations in Chronic Myelomonocytic Leukemia Undergoing Allogeneic Stem Cell Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1713-1713 ◽  
Author(s):  
Nico Gagelmann ◽  
Anita Badbaran ◽  
Rashit Bogdanov ◽  
Olivier Nibourel ◽  
Friedrich Stoelzel ◽  
...  
Keyword(s):  
High Risk ◽  
Genetic Risk ◽  
Research Funding ◽  
Risk Group ◽  
Performance Status ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Research Support ◽  
Total Cohort

Current risk stratification for newly diagnosed patients with chronic myelomonocytic leukemia (CMML) includes clinical and genetic features accounting for its variable disease course. Allogeneic stem cell transplantation still remains the only curative treatment option, and prognostication of posttransplant outcome may be improved using molecular information. Here, we aim to evaluate the molecular profile and its role on posttransplant outcome in a multicenter CMML cohort. Mutation analysis was performed on DNA from bone marrow mononuclear cells or peripheral granulocytes collected prior to transplant and included previously published CMML-associated genes (i.a. SETBP1, ASXL1, RUNX1, NRAS, KRAS, TET2, CBL, IDH1/2, SF3B1, DNMT3A, EZH2, ZRSR2, U2AF1). Current prognostic models were calculated at time of transplant. Patients with transformation to acute leukemia were excluded. Top predictors of posttransplant outcome were identified using the Random Forest algorithm. Main end points were overall survival (OS) and non-relapse mortality (NRM). The total cohort consisted of 185 patients of whom seven had CMML-0, 100 CMML-1, and 78 CMML-2 at time of transplant. The median follow-up was 74 months and 6-year OS was 37% for the total cohort and differed for CMML-0 (57%), CMML-1 (43%), and CMML-2 (29%). Relapse and NRM were 27% and 44% for the total cohort being 17% and 31% for CMML-0, 23% and 40% for CMML-1, and 34% and 40% for CMML-2. Most frequently mutated genes were: TET2 (55%), ASXL1 (41%), SF3B1 (38%), DNMT3A (27%), ZRSR2 (22%), NRAS (21%), EZH2 (21%), RUNX1 (17%), and SETBP1 (17%). Ninety-two percent of patients showed at least one somatic mutation. More than three mutations were present in 49% of all patients and in 29% of CMML-0, 50% of CMML-1, and 49% of CMML-2 patients. Frequencies according to CMML-specific prognostic scoring system (CPSS) and its molecular refinement (CPSS-mol) were 8% and 6% (low risk), 31% and 18% (intermediate-1 risk), 43% and 40% (intermediate-2 risk), and 18% and 36% (high risk). Transplants were received from matched unrelated (51%), mismatched unrelated (25%), matched related (21%), or mismatched related donors (3%). Conditioning intensity was reduced (49%), myeloablative (43%), or non-myeloablative (8%). Median age of patients was 60 years, 29% were female, 30% had a Karnofsky performance status <90%, and 15% had a comorbidity index >3. In the first step of the OS analysis, the algorithm identified mutations in ASXL1, KRAS, SF3B1, ZRSR2 as high-risk mutations (HRM) predicting worse OS. In addition, the number of the HRMs was associated with worse OS. In the next step, the algorithm automatically stratified this information into three distinct risk groups: the absence of HRMs (reference; low risk), presence of 1-2 HRMs (HR, 1.81; intermediate-risk), and 3-4 HRMs (HR, 2.93; high-risk). Corresponding 6-year OS was 59% for the low-risk, 34% for the intermediate-risk, and 14% for the high-risk group (P<.001; Figure 1A). Furthermore, the absence of HRMs was associated with lower NRM (15%) compared with present HRMs (46%; P=.01). In contrast, the CPSS-mol genetic risk classification including ASXL1, RUNX1, NRAS, and SETBP1 mutations showed no distinct 6-year OS or NRM (P=.15, respectively). Next, we adjusted the impact on OS of the proposed genetic risk for other factors included in the CPSS-mol. Higher genetic risk was independently associated with increased hazard for death (with the low-risk group as reference) showing HRs of 1.70 for the intermediate-risk and 2.83 for the high-risk group (P<.001). This model showed a concordance index of 0.633 versus CPSS-mol (0.597) or the CPSS (0.572) suggesting utility of transplant-specific prognostication. Therefore, we evaluated the multivariable effect on posttransplant outcome including the following independent clinical and molecular predictors: genetic risk, % of peripheral and bone marrow blasts, leukocyte count, and performance status. This model was predictive of OS and NRM (P<.001, respectively), and showed increased prognostic precision for OS, reflected in a concordance index of 0.684. In conclusion, mutations in ASXL1, KRAS, SF3B1, ZRSR2, and the number of these mutations predict OS and NRM in CMML undergoing transplantation. Accounting for these genetic lesions may improve the prognostic precision and patient counseling in the transplant setting. Figure 1 Disclosures Bogdanov: Jazz Pharmaceuticals, MSD.: Other: Travel subsidies. Stoelzel:Neovii: Other: Travel funding; JAZZ Pharmaceuticals: Consultancy; Shire: Consultancy, Other: Travel funding. Rautenberg:Jazz Pharmaceuticals: Other: Travel Support; Celgene: Honoraria, Other: Travel Support. Dreger:Neovii, Riemser: Research Funding; MSD: Membership on an entity's Board of Directors or advisory committees, Other: Sponsoring of Symposia; AbbVie, AstraZeneca, Gilead, Janssen, Novartis, Riemser, Roche: Consultancy; AbbVie, Gilead, Novartis, Riemser, Roche: Speakers Bureau. Finke:Riemser: Honoraria, Other: research support, Speakers Bureau; Neovii: Honoraria, Other: research support, Speakers Bureau; Medac: Honoraria, Other: research support, Speakers Bureau. Kobbe:Pfizer: Honoraria, Other: Travel support; Takeda: Honoraria, Other: Travel support; Celgene: Honoraria, Other: Travel support, Research Funding; Jazz: Honoraria, Other: Travel support; Amgen: Honoraria, Other: Travel support, Research Funding; Biotest: Honoraria, Other: Travel support; MSD: Honoraria, Other: Travel support; Neovii: Honoraria, Other: Travel support; Abbvie: Honoraria, Other: Travel support; Novartis: Honoraria, Other: Travel support; Roche: Honoraria, Other: Travel support; Medac: Honoraria, Other: Travel support. Platzbecker:Celgene: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding. Robin:Novartis Neovii: Research Funding. Beelen:Medac GmbH Wedel Germany: Consultancy, Honoraria. Kroeger:JAZZ: Honoraria; Neovii: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Sanofi-Aventis: Honoraria; Novartis: Honoraria, Research Funding; Medac: Honoraria; DKMS: Research Funding; Riemser: Research Funding.

scholarly journals Association between a Genetic Risk Score Based on Single Nucleotide Polymorphisms of Coronary Artery Disease-Related Genes and Left Main Coronary Artery Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Zhengxi Xu ◽  
Hanning Liu ◽  
Cheng Sun ◽  
Ke Si ◽  
Yan Zhao ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
High Risk ◽  
Risk Score ◽  
Genetic Risk ◽  
Risk Group ◽  
Genetic Risk Score ◽  
High Risk Group ◽  
Low Risk ◽  
Artery Disease

Coronary artery disease (CAD) is the leading cause of mortality and morbidity worldwide. Left main coronary artery disease (LMCAD) is a severe phenotype of CAD and has a genetic component. Previous studies identified 3 inflammation-related single nucleotide polymorphisms (SNPs) contributing to the development of LMCAD. We integrated these SNPs into a genetic risk score for the prediction of LMCAD. We enrolled 1544 patients with CAD between 2007 and 2011. The individual associations of the 3 SNPs with LMCAD were assessed. We then calculated the genetic risk score for each patient and stratified patients into low-risk, intermediate-risk, and high-risk categories of genetic risk. In univariable logistic regression analysis, the odds of LMCAD for the high-risk group were 2.81 (95% confidence interval [CI]: 1.72-4.60; P = 0.02) times those of the low-risk group. After adjustment for CAD-related clinical variables, the high-risk group (adjusted OR: 2.78; 95% CI: 1.69-4.58; P = 0.02) had increased odds of LMCAD when compared with the low-risk group. Comparison of model c-statistics showed greater predictive value with regard to LMCAD for the genetic risk score model than the models including single SNPs.

The UCLA Histo-Genetic Risk Classification (U-HGRC) to predict outcomes of localized clear cell renal cell carcinoma.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 627-627
Author(s):  
Cedric Michel Lebacle ◽  
Aydin Pooli ◽  
Nagesh Rao ◽  
Erika Louise Wood ◽  
Nils Kroeger ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
High Risk ◽  
Genetic Risk ◽  
Clear Cell ◽  
Risk Group ◽  
High Risk Group ◽  
Cell Renal Cell Carcinoma ◽  
Risk Of Recurrence ◽  
Random Samples

627 Background: Thirty percent of patients with localized clear cell renal cell carcinoma (ccRCC) will ultimately develop recurrence (local or metastatic) after nephrectomy. Current risk stratification systems still misclassify patients. We have developed a novel classification integrating cytogenetic findings to better stratify the risk of recurrence and overall survival (OS) after surgery for localized ccRCC. Methods: A total of 646 patients from UCLA with ccRCC and tumor cytogenetic analysis, were included in this study. After a selection of histologic parameters using logistic regression and cytogenetic parameters using principal component analysis a CHAID decision tree and Kaplan Meier analysis were used to build the UCLA Histo-Genetic Risk Classification (U-HGRC). Survival analyses of the model were validated on two random samples of 323 patients. Recurrence was defined as any local recurrence or development of new metastasis after surgery. Results: The T-stage, tumor size, presence of sarcomatoid features, gain of chromosome 5q, loss 10q, or loss X/Y were used to stratify the risk of recurrence of ccRCC into three U-HGRC groups of low (1), intermediate (2) or high-risk (3). After a mean follow-up of 55 months, risk of recurrence (HR = 2.44, p = .001 for U-HGRC 2; HR = 9.90, p < .0001 for U-HGRC 3), disease-free survival (DFS) (Log-rank p < .0001), risk of death (HR = 1.72, p = .033 for U-HGRC 2; HR = 4.74, p < .0001 for U-HGRC 3) and OS (Log-rank p < .0001) were significantly different between groups. These findings were validated on two random samples. For high-risk group, median DFS and OS were 2.7 and 6.3 years, respectively. The 5-year risks of recurrence for U-HGRC group 1, 2 and 3 were 9%, 25% and 62%, respectively. The AUC of the model was significantly improved comparing to the current UISS system (0.72 for U-HGRC vs 0.65 for UISS, p = .008) with an accuracy of 82.8% for the U-HGRC high-risk group. Conclusions: The U-HGRC, which integrates genomic alterations with clinical and pathologic features, allowed a better stratification of recurrence risk and overall survival that could help to select appropriate patients for surveillance and adjuvant therapy protocols.

UPAYA PERAWATAN KEHAMILAN DENGAN SENAM HAMIL PADA IBU HAMIL TRIMESTER III DI PUSKESMAS AMBAN MANOKWARI

2021 ◽  
Vol 2 (1) ◽  
pp. 29
Author(s):  
Yayuk Nuryanti
Keyword(s):  
High Risk ◽  
Pregnant Women ◽  
Health Center ◽  
Health Problem ◽  
Risk Group ◽  
Health Problems ◽  
High Risk Group ◽  
The Body ◽  
Reducing Stress ◽  
In Pregnancy

Pregnancy is a natural and physiological process that every woman experiences. Pregnant women are a high risk group for health problems. Stress is a health problem that often occurs in pregnant women. The goals of pregnancy exercise include reducing stress and preparing physically and psychologically for pregnant women. The purpose of the activity is to increase knowledge and empower pregnant women to care for their health independently. The method used is pregnancy exercise lectures and exercises. Participants in pregnancy exercise were 20 trimester III pregnant women. Implementing activities consisted of lecturers, health center midwives and students. The results of the activity were obtained through interviews which explained that participants learned about the benefits of pregnancy exercise, pregnancy exercise can make the body comfortable, and participants are interested in pregnancy exercise. The results of this activity can be concluded that the class of pregnant women must be held at the Puskesmas with activities such as pregnancy exercise.

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