scholarly journals Precision medicine screening using whole-genome sequencing and advanced imaging to identify disease risk in adults

2018 ◽  
Vol 115 (14) ◽  
pp. 3686-3691 ◽  
Author(s):  
Bradley A. Perkins ◽  
C. Thomas Caskey ◽  
Pamila Brar ◽  
Eric Dec ◽  
David S. Karow ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Chronic Diseases ◽  
Genome Sequencing ◽  
Disease Risk ◽  
Premature Mortality ◽  
Whole Genome ◽  
Clinical Testing ◽  
Advanced Imaging ◽  
Age Related ◽  
Disease Risks

Reducing premature mortality associated with age-related chronic diseases, such as cancer and cardiovascular disease, is an urgent priority. We report early results using genomics in combination with advanced imaging and other clinical testing to proactively screen for age-related chronic disease risk among adults. We enrolled active, symptom-free adults in a study of screening for age-related chronic diseases associated with premature mortality. In addition to personal and family medical history and other clinical testing, we obtained whole-genome sequencing (WGS), noncontrast whole-body MRI, dual-energy X-ray absorptiometry (DXA), global metabolomics, a new blood test for prediabetes (Quantose IR), echocardiography (ECHO), ECG, and cardiac rhythm monitoring to identify age-related chronic disease risks. Precision medicine screening using WGS and advanced imaging along with other testing among active, symptom-free adults identified a broad set of complementary age-related chronic disease risks associated with premature mortality and strengthened WGS variant interpretation. This and other similarly designed screening approaches anchored by WGS and advanced imaging may have the potential to extend healthy life among active adults through improved prevention and early detection of age-related chronic diseases (and their risk factors) associated with premature mortality.

scholarly journals Precision Medicine Screening Using Whole Genome Sequencing and Advanced Imaging To Identify Disease Risk in Adults

2017 ◽  
Author(s):  
Bradley A Perkins ◽  
C. Thomas Caskey ◽  
Pamila Brar ◽  
Eric Dec ◽  
David Karow ◽  
...  
Keyword(s):  
Early Detection ◽  
Whole Genome Sequencing ◽  
Chronic Diseases ◽  
Genome Sequencing ◽  
Clinical Data ◽  
Premature Mortality ◽  
Medical Attention ◽  
Whole Genome ◽  
Age Related ◽  
Active Adults

ABSTRACTBACKGROUNDProgress in science and technology have created the capabilities and alternatives to symptom-driven medical care. Reducing premature mortality associated with age-related chronic diseases, such as cancer and cardiovascular disease, is an urgent priority we address using advanced screening detection.METHODSWe enrolled active adults for early detection of risk for age-related chronic disease associated with premature mortality. Whole genome sequencing together with: global metabolomics, 3D/4D imaging using non-contrast whole body magnetic resonance imaging and echocardiography, and 2-week cardiac monitoring were employed to detect age-related chronic diseases and risk for diseases.RESULTSWe detected previously unrecognized age-related chronic diseases requiring prompt (<30 days) medical attention in 17 (8%, 1:12) of 209 study participants, including 4 participants with early stage neoplasms (2%, 1:50). Likely mechanistic genomic findings correlating with clinical data were identified in 52 participants (25%. 1:4). More than three-quarters of participants (n=164, 78%, 3:4) had evidence of age-related chronic diseases or associated risk factors.CONCLUSIONSPrecision medicine screening using genomics with other advanced clinical data among active adults identified unsuspected disease risks for age-related chronic diseases associated with premature mortality. This technology-driven phenotype screening approach has the potential to extend healthy life among active adults through improved early detection and prevention of age-related chronic diseases. Our success provides a scalable strategy to move medical practice and discovery toward risk detection and disease modification thus achieving healthier extension of life.SIGNIFICANCE STATEMENTAdvances in science and technology have enabled scientists to analyze the human genome cost-effectively and to combine genome sequencing with noninvasive imaging technologies for alternatives to symptom-driven medical care. Using whole genome sequencing and noninvasive 3D/4D imaging technologies we screened 209 adults to detect age-related chronic diseases, such as cancer and cardiovascular disease. We found unrecognized age-related chronic diseases requiring prompt (<30 days) medical attention in 1:12 study participants, likely genomic findings correlating with clinical data in 1:4 participants, and evidence of age-related chronic diseases or associated risk factors in more than 3 of 4 participants. These results demonstrate that genome sequencing with clinical imaging data can be used for screening and early detection of diseases associated with premature mortality.

scholarly journals Effects of supplementation with carnosine and other histidine-containing dipeptides on chronic disease risk factors and outcomes: protocol for a systematic review of randomised controlled trials

BMJ Open ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. e020623 ◽  
Author(s):  
Kirthi Menon ◽  
Aya Mousa ◽  
Barbora de Courten
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Chronic Disease ◽  
Chronic Diseases ◽  
Randomised Controlled Trials ◽  
Disease Risk ◽  
Primary Data ◽  
Controlled Trials ◽  
Chronic Disease Risk ◽  
Randomised Controlled

IntroductionAgeing of populations globally, coupled with the obesity epidemic, has resulted in the rising prevalence of chronic diseases including diabetes, cardiovascular diseases, cancers and neurodegenerative disorders. Prevention of risk factors that contribute to these diseases is key in managing the global burden of chronic diseases. Recent studies suggest that carnosine, a dipeptide with anti-inflammatory, antioxidative and antiglycating properties may have a role in the prevention of chronic diseases; however, no previous reviews have examined the effects of carnosine and other histidine-containing peptides (HCDs) on chronic disease risk factors and outcomes. We aim to conduct a comprehensive systematic review to examine the effects of supplementation with carnosine and other HCDs on chronic disease risk factors and outcomes and to identify relevant knowledge gaps.Methods and analysisElectronic databases including Medline, Cumulative Index of Nursing and Allied Health, Embase and all Evidence-Based Medicine will be systematically searched to identify randomised controlled trials (RCTs) and systematic reviews of RCTs, comparing supplementation with carnosine and/or other HCDs versus placebo, usual care or other pharmacological or non-pharmacological interventions. One reviewer will screen titles and abstracts for eligibility according to prespecified inclusion criteria, after which two independent reviewers will perform data extraction and quality appraisal. Meta-analyses, metaregression and subgroup analyses will be conducted where appropriate.Ethics and disseminationEthics approval is not required as this review does not involve primary data collection. This review will generate level-one evidence regarding the effects of carnosine supplementation on chronic disease risk factors and outcomes and will be disseminated through peer-reviewed publications and at conference meetings to inform future research on the efficacy of carnosine supplementation for the prevention of chronic diseases.PROSPERO registration numberCRD42017075354.

Red Meat and Health

2016 ◽  
pp. 131-177 ◽  
Author(s):  
Kate Marsh ◽  
Angela Saunders ◽  
Carol Zeuschner
Keyword(s):  
Chronic Disease ◽  
Chronic Diseases ◽  
Disease Risk ◽  
Red Meat ◽  
Current Evidence ◽  
Processed Meat ◽  
Mortality Risks ◽  
Regular Consumption ◽  
Health And Disease ◽  
Nutritional Benefits

Despite its nutritional benefits, there is an increasing body of evidence to suggest that regular consumption of red meat may negatively impact health and disease risk, including the risk of most common chronic diseases. This chapter reviews the current evidence linking red and processed meat intakes with chronic disease, obesity and mortality risks and discusses possible mechanisms to explain these associations. Research on the health benefits of diets low in red meat, including vegetarian, vegan, Mediterranean and other plant-based diets, is also reviewed.

scholarly journals Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging

2020 ◽  
Vol 117 (6) ◽  
pp. 3053-3062 ◽  
Author(s):  
Ying-Chen Claire Hou ◽  
Hung-Chun Yu ◽  
Rick Martin ◽  
Elizabeth T. Cirulli ◽  
Natalie M. Schenker-Ahmed ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Precision Medicine ◽  
Genome Sequencing ◽  
Clinical Laboratory ◽  
Descriptive Analysis ◽  
Disease Diagnosis ◽  
Whole Genome ◽  
Advanced Imaging ◽  
Family Medical History ◽  
Deep Phenotyping

Genome sequencing has established clinical utility for rare disease diagnosis. While increasing numbers of individuals have undergone elective genome sequencing, a comprehensive study surveying genome-wide disease-associated genes in adults with deep phenotyping has not been reported. Here we report the results of a 3-y precision medicine study with a goal to integrate whole-genome sequencing with deep phenotyping. A cohort of 1,190 adult participants (402 female [33.8%]; mean age, 54 y [range 20 to 89+]; 70.6% European) had whole-genome sequencing, and were deeply phenotyped using metabolomics, advanced imaging, and clinical laboratory tests in addition to family/medical history. Of 1,190 adults, 206 (17.3%) had at least 1 genetic variant with pathogenic (P) or likely pathogenic (LP) assessment that suggests a predisposition of genetic risk. A multidisciplinary clinical team reviewed all reportable findings for the assessment of genotype and phenotype associations, and 137 (11.5%) had genotype and phenotype associations. A high percentage of genotype and phenotype associations (>75%) was observed for dyslipidemia (n = 24), cardiomyopathy, arrhythmia, and other cardiac diseases (n = 42), and diabetes and endocrine diseases (n = 17). A lack of genotype and phenotype associations, a potential burden for patient care, was observed in 69 (5.8%) individuals with P/LP variants. Genomics and metabolomics associations identified 61 (5.1%) heterozygotes with phenotype manifestations affecting serum metabolite levels in amino acid, lipid and cofactor, and vitamin pathways. Our descriptive analysis provides results on the integration of whole-genome sequencing and deep phenotyping for clinical assessments in adults.

scholarly journals Desexing Dogs: A Review of the Current Literature

Animals ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 1086 ◽  
Author(s):  
Silvan R. Urfer ◽  
Matt Kaeberlein
Keyword(s):  
Beneficial Effect ◽  
Disease Risk ◽  
Population Control ◽  
Cruciate Ligament ◽  
Empirical Studies ◽  
Alternative Methods ◽  
Control Effect ◽  
Age Related ◽  
Ultimate Cause ◽  
Disease Risks

Background: Desexing dogs is promoted for population control, preventative healthcare, and behavior modification. Common methods are orchiectomy and ovariectomy/ovariohysterectomy. GnRH superagonist implants are available in some areas. Alternative methods like vasectomy and salpingectomy/hysterectomy are uncommon. The terminology used to describe desexing is inconsistent and contradictory, showing a need for the adaption of standardized terminology. Population Control: Surprisingly, empirical studies show no effects of desexing on population control in companion and shelter dogs despite desexing being consistently recommended in the literature. There is evidence for a population control effect in free-roaming dogs, where desexing also has benefits on zoonotic disease and bite risk. Population control in free-roaming dogs is mostly correlated with female, not male desexing. Health and Lifespan: Desexing affects numerous disease risks, but studies commonly neglect age at diagnosis and overall lifespan, age being by far the most important risk factor for most diseases. We argue that lifespan is a more important outcome than ultimate cause of death. A beneficial effect of desexing on lifespan is consistently demonstrated in females, while evidence for a beneficial effect in males is inconsistent. Studies are likely biased in desexing being a proxy for better care and desexed dogs having already lived to the age of desexing. Desexing reduces or eliminates common life-limiting diseases of the female reproductive system such as pyometra and mammary tumors, while no analogous effect exists in males. Disease risks increases across sexes and breeds include cruciate ligament rupture, various cancers, and obesity. Urinary incontinence risk is increased in females only. Various other disease risk changes show considerable variability between breeds and sexes. Behavioral Effects: Desexed males show reduced libido, roaming, conspecific mounting, and urinary marking frequency, as well as reduced male dog-directed aggression in a majority of males desexed for behavioral reasons. There is a detrimental effect on the risk and progression of age-related cognitive dysfunction. Desexed dogs may be less likely to cause bite injuries across sexes. The evidence for other effects such as human-directed aggression, human or object mounting, resource guarding, or shyness and anxiety is inconsistent and contradictory. There are few studies specific to females or individual breeds. Conclusions: The evidence for a beneficial effect of desexing is stronger in female than in male dogs; however, there is significant variation between breeds and sexes, and more research is needed to further elucidate these differences and to arrive at individualized evidence-based recommendations for clinical practice.

scholarly journals The relationship between total plasma carotenoids and risk factors for chronic disease among middle-aged and older men

2008 ◽  
Vol 100 (4) ◽  
pp. 883-889 ◽  
Author(s):  
Wildon R. Farwell ◽  
J. Michael Gaziano ◽  
Edward P. Norkus ◽  
Howard D. Sesso
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Chronic Disease ◽  
Chronic Diseases ◽  
Disease Risk ◽  
Alcohol Ingestion ◽  
Health Study ◽  
Parameter Estimates ◽  
Total Plasma ◽  
The Relationship

Individual plasma carotenoids have been associated with various chronic diseases but little is known about the relationship between total plasma carotenoids and risk factors for chronic diseases. In the Physicians' Health Study, we examined 492 men free of CVD and cancer for the relationship between total plasma carotenoids (the sum of α-carotene, β-carotene, lycopene, zeaxanthin, lutein and β-cryptoxanthin) and a wide variety of factors that predict chronic disease. Multivariate linear and logistic regression was performed to calculate parameter estimates (95 % CI) and OR (95 % CI) for total plasma carotenoids. In linear regression models, BMI, hypertension, alcohol intake and plasma levels of each lipid parameter and α-tocopherol significantly predicted levels of total plasma carotenoids. Upon adjustment for multiple chronic disease risk factors, the OR for levels of total plasma carotenoids greater than or equal to the median ( ≥ 1·301 μmol/l) was statistically significant for current smoking (OR 0·21; 95 % CI 0·06, 0·77), weekly alcohol ingestion (OR 2·30; 95 % CI 1·06, 4·99), daily alcohol ingestion (OR 2·46; 95 % CI 1·29, 4·67), each 100 mg/l increase in total cholesterol (OR 0·73; 95 % CI 0·58, 0·91), LDL-cholesterol (OR 1·48; 95 % CI 1·17, 1·89) and HDL-cholesterol (OR 1·58; 95 % CI 1·26, 1·99), each 100 mg/ml increase in intercellular adhesion molecule-1 (OR 0·70; 95 % CI 0·53, 0·93) and each 10 μmol/l increase in α-tocopherol (OR 1·33; 95 % CI 1·12, 1·57), using logistic regression. Few lifestyle and clinical risk factors appear to be related to levels of total plasma carotenoids; however, levels of biomarkers such as plasma lipids and α-tocopherol may be strongly related.

scholarly journals Ketogenic Diets and Chronic Disease: Weighing the Benefits Against the Risks

2021 ◽  
Vol 8 ◽  
Author(s):  
Lee Crosby ◽  
Brenda Davis ◽  
Shivam Joshi ◽  
Meghan Jardine ◽  
Jennifer Paul ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Chronic Diseases ◽  
Diet Quality ◽  
Disease Risk ◽  
Epidemiological Studies ◽  
Short Term ◽  
Chronic Disease Risk ◽  
Ketogenic Diets ◽  
Low Carbohydrate

Very-low-carbohydrate ketogenic diets have been long been used to reduce seizure frequency and more recently have been promoted for a variety of health conditions, including obesity, diabetes, and liver disease. Ketogenic diets may provide short-term improvement and aid in symptom management for some chronic diseases. Such diets affect diet quality, typically increasing intake of foods linked to chronic disease risk and decreasing intake of foods found to be protective in epidemiological studies. This review examines the effects of ketogenic diets on common chronic diseases, as well as their impact on diet quality and possible risks associated with their use. Given often-temporary improvements, unfavorable effects on dietary intake, and inadequate data demonstrating long-term safety, for most individuals, the risks of ketogenic diets may outweigh the benefits.

scholarly journals Novel Alzheimer’s disease risk variants identified based on whole-genome sequencing of APOE ε4 carriers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jong-Ho Park ◽  
Inho Park ◽  
Emilia Moonkyung Youm ◽  
Sejoon Lee ◽  
June-Hee Park ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Disease Risk ◽  
Association Studies ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Whole Genome ◽  
Ε4 Allele

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disease associated with a complex genetic etiology. Besides the apolipoprotein E ε4 (APOE ε4) allele, a few dozen other genetic loci associated with AD have been identified through genome-wide association studies (GWAS) conducted mainly in individuals of European ancestry. Recently, several GWAS performed in other ethnic groups have shown the importance of replicating studies that identify previously established risk loci and searching for novel risk loci. APOE-stratified GWAS have yielded novel AD risk loci that might be masked by, or be dependent on, APOE alleles. We performed whole-genome sequencing (WGS) on DNA from blood samples of 331 AD patients and 169 elderly controls of Korean ethnicity who were APOE ε4 carriers. Based on WGS data, we designed a customized AD chip (cAD chip) for further analysis on an independent set of 543 AD patients and 894 elderly controls of the same ethnicity, regardless of their APOE ε4 allele status. Combined analysis of WGS and cAD chip data revealed that SNPs rs1890078 (P = 6.64E−07) and rs12594991 (P = 2.03E−07) in SORCS1 and CHD2 genes, respectively, are novel genetic variants among APOE ε4 carriers in the Korean population. In addition, nine possible novel variants that were rare in individuals of European ancestry but common in East Asia were identified. This study demonstrates that APOE-stratified analysis is important for understanding the genetic background of AD in different populations.

scholarly journals Distinguishing Relapse From Reinfection With Whole-Genome Sequencing in Recurrent Pulmonary Tuberculosis: A Retrospective Cohort Study in Beijing, China

2021 ◽  
Vol 12 ◽  
Author(s):  
Jian Du ◽  
Qing Li ◽  
Min Liu ◽  
Yufeng Wang ◽  
Zhongtan Xue ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Chronic Diseases ◽  
Genome Sequencing ◽  
Strong Association ◽  
Drug Susceptibility ◽  
Diabetic Patients ◽  
Whole Genome ◽  
Community Transmission ◽  
Susceptibility Profiles ◽  
Beijing China

Background: Tuberculosis recurrence is still a major problem for the control of tuberculosis, and the cause of the recurrence is still unclear.Methods: We retrospectively recruited 68 pairs of samples of Mycobacterium tuberculosis (MTB) from recurrent TB cases in Beijing Chest Hospital between January 2008 and December 2019. The whole-genome sequencing was conducted to analyze single-nucleotide polymorphism (SNP) and to identify whether recurrent disease was due to relapse or reinfection. The BACTEC MGIT was performed to compare differences in drug susceptibility profiles between two episodes.Results: 62 (91.2%) out of 68 confirmed recurrence were due to relapse, whereas the remaining six (8.8%) were due to reinfection. And there was a strong association between earlier relapse and underlying chronic diseases. In addition, the MTB isolates from non-diabetic patients had a higher mutation rate than those from diabetic patients. A community transmission was also identified in our cohort. Levofloxacin resistance was the most frequently observed drug resistance for 12.9% relapse cases.Conclusion: The relapse of a previous episode in Beijing. The underlying chronic diseases are associated with an earlier TB relapse. MTB isolates were more prone to develop levofloxacin resistance than moxifloxacin resistance after FQ exposure. The patients at high-risk for relapses deserve more careful investigation.

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