Biobanks, Association Studies and Validity: Ethical, Legal and Social Challenges in Asia

2007 ◽  
Vol 4 (4) ◽  
Author(s):  
Minakshi Bhardwaj
Keyword(s):  
Cohort Studies ◽  
Genetic Information ◽  
Association Studies ◽  
Genomic Data ◽  
Clinical Information ◽  
Population Based ◽  
Genome Project ◽  
Biological Research ◽  
Genetic Database ◽  
The Uk

AbstractScientists are making attempts to develop a detailed understanding of the heritable variation in the human genome at individual and population level. It is claimed that population based genomics research will be crucial in understanding the differences in the human susceptibility to diseases, drug responses and the complex interaction of genetic and environmental factors in the production of particular phenotypes (DoH white paper 2003). These efforts led to the phenomenon of biobanking and setting up mega- genetic databases. Since the development of the Icelandic Health Sector Database, the biobanking phenomenon is taking up pace and several countries of the world are starting several large-scale population based genomics projects under the umbrella of biobanking and genetic databases. At the time of an increased interest in acquiring information on gene-gene interactions and gene-environmental interactions, it is important to acknowledge that although promising, these prospects face major scientific hurdles and ethical questions in practice. The definitions, applications and prospective implications of genetic databases and biobanks on health and healthcare are understood and implied in several ways both in clinical and biological research. The term genetic database can imply to a collection of biological material (biobank) from which genetic information, for example genealogical and clinical information can be derived, systematically organized and used for research purposes. Different countries have used different terminologies for their collections of biological materials and have organised genetic information in large databases. Sometimes the term biobank also includes a complex network of databases assembled and accredited in one system. COGENE, the ‘Coordination of Genome Research Across Europe’ refers to biobanks as cohort studies. Cohort studies involve comparative studies between a diseased group with some common parameters such as geography, age, employment, a disease condition or any other determinant within a general group. The groups are compared for a long period of time for specific tests. For instance, the unified database of the Latvian Population is popularly called the Latvian Genome Project. The Latvian Project aims to create ‘a unified national network of genetic information and data processing, to collect representative amount of genetic material for genotyping of the Latvian population and to compare genomic data with the clinical information and the information available about specific pedigrees’ (Pirags and Grens 2005). Genomic data will contain the sum-total of genetic information in the entire DNA of the Latvian population. Other examples are the UK population-based genetic database, which has started under the name of the UK Biobank. It involves systematic collections of biological samples and medical and genetic information. The Estonian Genome Project uses the concept of Gene bank to refer to its genetic database. Gene banks and genomic banks are similar in that they contain large sets of genetic information in the form of datasets and sequences of the population.

scholarly journals Use of SNP chips to detect rare pathogenic variants: retrospective, population based diagnostic evaluation

BMJ ◽  
2021 ◽  
pp. n214
Author(s):  
Weedon MN ◽  
Jackson L ◽  
Harrison JW ◽  
Ruth KS ◽  
Tyrrell J ◽  
...  
Keyword(s):  
Positive Predictive Value ◽  
Predictive Value ◽  
Population Based ◽  
Genome Project ◽  
Personal Genome ◽  
Uk Biobank ◽  
Sequencing Data ◽  
Snp Chip ◽  
Pathogenic Variants ◽  
The Uk

Abstract Objective To determine whether the sensitivity and specificity of SNP chips are adequate for detecting rare pathogenic variants in a clinically unselected population. Design Retrospective, population based diagnostic evaluation. Participants 49 908 people recruited to the UK Biobank with SNP chip and next generation sequencing data, and an additional 21 people who purchased consumer genetic tests and shared their data online via the Personal Genome Project. Main outcome measures Genotyping (that is, identification of the correct DNA base at a specific genomic location) using SNP chips versus sequencing, with results split by frequency of that genotype in the population. Rare pathogenic variants in the BRCA1 and BRCA2 genes were selected as an exemplar for detailed analysis of clinically actionable variants in the UK Biobank, and BRCA related cancers (breast, ovarian, prostate, and pancreatic) were assessed in participants through use of cancer registry data. Results Overall, genotyping using SNP chips performed well compared with sequencing; sensitivity, specificity, positive predictive value, and negative predictive value were all above 99% for 108 574 common variants directly genotyped on the SNP chips and sequenced in the UK Biobank. However, the likelihood of a true positive result decreased dramatically with decreasing variant frequency; for variants that are very rare in the population, with a frequency below 0.001% in UK Biobank, the positive predictive value was very low and only 16% of 4757 heterozygous genotypes from the SNP chips were confirmed with sequencing data. Results were similar for SNP chip data from the Personal Genome Project, and 20/21 individuals analysed had at least one false positive rare pathogenic variant that had been incorrectly genotyped. For pathogenic variants in the BRCA1 and BRCA2 genes, which are individually very rare, the overall performance metrics for the SNP chips versus sequencing in the UK Biobank were: sensitivity 34.6%, specificity 98.3%, positive predictive value 4.2%, and negative predictive value 99.9%. Rates of BRCA related cancers in UK Biobank participants with a positive SNP chip result were similar to those for age matched controls (odds ratio 1.31, 95% confidence interval 0.99 to 1.71) because the vast majority of variants were false positives, whereas sequence positive participants had a significantly increased risk (odds ratio 4.05, 2.72 to 6.03). Conclusions SNP chips are extremely unreliable for genotyping very rare pathogenic variants and should not be used to guide health decisions without validation.

scholarly journals Cardiometabolic risk factors for COVID-19 susceptibility and severity: A Mendelian randomization analysis

PLoS Medicine ◽  
2021 ◽  
Vol 18 (3) ◽  
pp. e1003553
Author(s):  
Aaron Leong ◽  
Joanne B. Cole ◽  
Laura N. Brenner ◽  
James B. Meigs ◽  
Jose C. Florez ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Statistical Significance ◽  
Epidemiological Studies ◽  
Population Based ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
The Uk

Background Epidemiological studies report associations of diverse cardiometabolic conditions including obesity with COVID-19 illness, but causality has not been established. We sought to evaluate the associations of 17 cardiometabolic traits with COVID-19 susceptibility and severity using 2-sample Mendelian randomization (MR) analyses. Methods and findings We selected genetic variants associated with each exposure, including body mass index (BMI), at p < 5 × 10−8 from genome-wide association studies (GWASs). We then calculated inverse-variance-weighted averages of variant-specific estimates using summary statistics for susceptibility and severity from the COVID-19 Host Genetics Initiative GWAS meta-analyses of population-based cohorts and hospital registries comprising individuals with self-reported or genetically inferred European ancestry. Susceptibility was defined as testing positive for COVID-19 and severity was defined as hospitalization with COVID-19 versus population controls (anyone not a case in contributing cohorts). We repeated the analysis for BMI with effect estimates from the UK Biobank and performed pairwise multivariable MR to estimate the direct effects and indirect effects of BMI through obesity-related cardiometabolic diseases. Using p < 0.05/34 tests = 0.0015 to declare statistical significance, we found a nonsignificant association of genetically higher BMI with testing positive for COVID-19 (14,134 COVID-19 cases/1,284,876 controls, p = 0.002; UK Biobank: odds ratio 1.06 [95% CI 1.02, 1.10] per kg/m2; p = 0.004]) and a statistically significant association with higher risk of COVID-19 hospitalization (6,406 hospitalized COVID-19 cases/902,088 controls, p = 4.3 × 10−5; UK Biobank: odds ratio 1.14 [95% CI 1.07, 1.21] per kg/m2, p = 2.1 × 10−5). The implied direct effect of BMI was abolished upon conditioning on the effect on type 2 diabetes, coronary artery disease, stroke, and chronic kidney disease. No other cardiometabolic exposures tested were associated with a higher risk of poorer COVID-19 outcomes. Small study samples and weak genetic instruments could have limited the detection of modest associations, and pleiotropy may have biased effect estimates away from the null. Conclusions In this study, we found genetic evidence to support higher BMI as a causal risk factor for COVID-19 susceptibility and severity. These results raise the possibility that obesity could amplify COVID-19 disease burden independently or through its cardiometabolic consequences and suggest that targeting obesity may be a strategy to reduce the risk of severe COVID-19 outcomes.

scholarly journals A Complete Public Domain Family Genomics Dataset

2013 ◽  
Author(s):  
Manuel Corpas ◽  
Mike Cariaso ◽  
Alain Coletta ◽  
David Weiss ◽  
Andrew P Harrison ◽  
...  
Keyword(s):  
Association Studies ◽  
Genomic Data ◽  
Public Domain ◽  
Negative Control ◽  
Genome Project ◽  
Family Data ◽  
Metagenomic Data ◽  
Personal Genome ◽  
Personal Genomics ◽  
Sequencing Data

BACKGROUND: The availability of open access genomic data is essential for the personal genomics field. Public genomic data allow comparative analyses, testing of new tools and genotype-phenotype association studies. Personal genomics data of unrelated individuals are available in the public domain, notably the Personal Genome Project; however, to date genomics family data and metadata are severely lacking, mainly due to cost, privacy concerns or restricted access to Next Generation Sequencing (NGS) technology. Family data have a lot to offer as they allow the study of heritability, something which is impossible to do just by using unrelated individuals. FINDINGS: A whole family from Southern Spain decided to genotype, sequence and analyse their personal genomes making them publicly available under a Creative Commons 0 license (CC0; commonly denominated as public domain). These data include a) five 23andMe SNP chip genotype bed files, b) four raw exomes with their assorted bam files and VCF files, c) a metagenomic raw sequencing data file and d) derived data of likely phenotypes using SNPedia-derived tools. CONCLUSIONS: To our knowledge this is the first CC0 released set of genomic, phenotypic and metagenomic data for a whole family. This dataset is also unique in that it was obtained through direct-to-consumer genetic tests. Hence any ordinary citizen with enough budget and samples should be able to reproduce this experiment. We envisage this dataset to be a useful resource for a variety of applications in the personal genomics field as a) negative control data for trait association discovery, b) testing data for development of new software and c) sample data for heritability studies. We encourage prospective users to share with us derived results so that they can be added to our existing collection.

Biobanks and Legislation in Switzerland – a data protection perspective

2007 ◽  
Vol 4 (5) ◽  
Author(s):  
Claudia Mund
Keyword(s):  
Medical Records ◽  
Population Based ◽  
Genome Project ◽  
Genetic Interactions ◽  
Government Support ◽  
Uk Biobank ◽  
Large Section ◽  
Homogeneous Population ◽  
Set Up ◽  
The Uk

AbstractThe combination of health and lifestyle data with bodily substances and genetic information has led over the last few years to the creation of so-called biobanks. These biobanks are used to research a large number of diseases of modern civilization and their genetic interactions. One of the best-known projects in this respect is without a doubt the Icelandic biobank, operated since 1998 by a private pharmaceutical company, deCode Genetics, and set up with government support. The database contains family histories and medical records, as well as biological samples taken from a large section of Iceland's homogeneous population. The hope is that this data will allow a correlation to be established between genetic predispositions and the onset of widespread diseases. Other examples of population-based biobanks include the Estonian Genome Project, launched in 2001 by the Estonian Government, as well as the UK Biobank in the UK and PopGen in the state of Schleswig-Holstein in Germany.

Ethnic Differences in Self-Poisoning Across South London

Crisis ◽  
2014 ◽  
Vol 35 (4) ◽  
pp. 268-272
Author(s):  
Sean Cross ◽  
Dinesh Bhugra ◽  
Paul I. Dargan ◽  
David M. Wood ◽  
Shaun L. Greene ◽  
...  
Keyword(s):  
Black Women ◽  
Data Collection ◽  
White Women ◽  
Population Based ◽  
Care Services ◽  
Self Harm ◽  
Managing Risk ◽  
The Uk ◽  
Incident Cases ◽  
Minority Ethnic

Background: Self-poisoning (overdose) is the commonest form of self-harm cases presenting to acute secondary care services in the UK, where there has been limited investigation of self-harm in black and minority ethnic communities. London has the UK’s most ethnically diverse areas but presents challenges in resident-based data collection due to the large number of hospitals. Aims: To investigate the rates and characteristics of self-poisoning presentations in two central London boroughs. Method: All incident cases of self-poisoning presentations of residents of Lambeth and Southwark were identified over a 12-month period through comprehensive acute and mental health trust data collection systems at multiple hospitals. Analysis was done using STATA 12.1. Results: A rate of 121.4/100,000 was recorded across a population of more than half a million residents. Women exceeded men in all measured ethnic groups. Black women presented 1.5 times more than white women. Gender ratios within ethnicities were marked. Among those aged younger than 24 years, black women were almost 7 times more likely to present than black men were. Conclusion: Self-poisoning is the commonest form of self-harm presentation to UK hospitals but population-based rates are rare. These results have implications for formulating and managing risk in clinical services for both minority ethnic women and men.

Strong Association between Serotonin Transporter 5-HTTVNTR Variant and Psychoactive Substance (Nicotine) Use in the Turkish Cypriot Population

2020 ◽  
Vol 21 (6) ◽  
pp. 466-470
Author(s):  
Emine Kandemis ◽  
Gulten Tuncel ◽  
Ozen Asut ◽  
Sehime G. Temel ◽  
Mahmut C. Ergoren
Keyword(s):  
Serotonin Transporter ◽  
Association Studies ◽  
Strong Association ◽  
Smoking Behavior ◽  
Population Based ◽  
Genome Wide Association Studies ◽  
Genotype Distribution ◽  
Psychological Traits ◽  
Wide Range ◽  
Turkish Cypriot

Background: The use of psychoactive substances is one of the most dangerous social problems worldwide. Nicotine dependence results from the interaction between neurobiological, environmental and genetic factors. Serotonin is a neurotransmitter that has a wide range of central nervous system activities. The serotonin transporter gene has been previously linked to psychological traits. Objective: A variable number of tandem repeats within the serotonin transporter-linked polymorphic gene region are believed to alter the transcriptional efficiency of the 5-HTT gene. Therefore, we aimed to investigate the association between this polymorphic site and smoking behavior in the Turkish Cypriot population. Methods: A total of 259 (100 smokers, 100 non-smokers and 59 ex-smokers) Turkish Cypriots were included in this population-based cross-sectional study. Genomic DNA was extracted from peripheral blood samples and the 5-HTTVNTR2 polymorphisms were determined by the PCR-RFLP. Results: The allelic frequency and genotype distribution results of this study showed a strong association (P<0.0001) between smokers and non-smokers. No statistical significance was found between non-smokers and ex-smokers. Conclusion: This is the first genetic epidemiology study to investigate the allelic frequencies of 5-HTTVNTR2 polymorphisms associated with smoking behavior in the Turkish Cypriot population. Based on the results of this study, genome-wide association studies should be designed for preventive medicine in this population.

scholarly journals Population screening for glaucoma in UK: current recommendations and future directions

Eye ◽  
2021 ◽  
Author(s):  
Sana Hamid ◽  
Parul Desai ◽  
Pirro Hysi ◽  
Jennifer M. Burr ◽  
Anthony P. Khawaja
Keyword(s):  
Screening Test ◽  
Vision Loss ◽  
Open Angle Glaucoma ◽  
Public Awareness ◽  
Population Based ◽  
Population Screening ◽  
Effective Population ◽  
Future Directions ◽  
The Future ◽  
The Uk

AbstractEffective population screening for glaucoma would enable earlier diagnosis and prevention of irreversible vision loss. The UK National Screening Committee (NSC) recently published a review that examined the viability, effectiveness and appropriateness of a population-based screening programme for primary open-angle glaucoma (POAG). In our article, we summarise the results of the review and discuss some future directions that may enable effective population screening for glaucoma in the future. Two key questions were addressed by the UK NSC review; is there a valid, accurate screening test for POAG, and does evidence exist that screening reduces morbidity from POAG compared with standard care. Six new studies were identified since the previous 2015 review. The review concluded that screening for glaucoma in adults is not recommended because there is no clear evidence for a sufficiently accurate screening test or for better outcomes with screening compared to current care. The next UK NSC review is due to be conducted in 2023. One challenge for POAG screening is that the relatively low disease prevalence results in too many false-positive referrals, even with an accurate test. In the future, targeted screening of a population subset with a higher prevalence of glaucoma may be effective. Recent developments in POAG polygenic risk prediction and deep learning image analysis offer potential avenues to identifying glaucoma-enriched sub-populations. Until such time, opportunistic case finding through General Ophthalmic Services remains the primary route for identification of glaucoma in the UK and greater public awareness of the service would be of benefit.

scholarly journals Analysing electrocardiographic traits and predicting cardiac risk in UK biobank

2021 ◽  
Vol 10 ◽  
pp. 204800402110236
Author(s):  
Julia Ramírez ◽  
Stefan van Duijvenboden ◽  
William J Young ◽  
Michele Orini ◽  
Aled R Jones ◽  
...  
Keyword(s):  
Genetic Information ◽  
Association Studies ◽  
Cardiac Risk ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Biological Mechanisms ◽  
Clinical Tool ◽  
Genome Wide ◽  
Response To Exercise ◽  
Electrocardiogram Ecg

The electrocardiogram (ECG) is a commonly used clinical tool that reflects cardiac excitability and disease. Many parameters are can be measured and with the improvement of methodology can now be quantified in an automated fashion, with accuracy and at scale. Furthermore, these measurements can be heritable and thus genome wide association studies inform the underpinning biological mechanisms. In this review we describe how we have used the resources in UK Biobank to undertake such work. In particular, we focus on a substudy uniquely describing the response to exercise performed at scale with accompanying genetic information.

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