Impact Of Genetic Information Research Articles

Informed consent and participant protection in human biodatabases: present and future

<p>近年來，由於精準醫療發展的需求，帶動生物醫學研究蓬勃發展，以人口群或疾病罹患者群體為基礎的人體生物資料庫（biobank）因為同時蒐集生物檢體、基因資訊與醫療資料，可大量節省研究者於研究過程招募受試者的時間成本，而可方便於串連不同來源的生物或醫療資訊，因而越來受到重視。就生物資料庫的參與者自主權保障而言，取得參與者的知情同意（informed consent），與其他人體研究略有不同。其不同之處在於，生物資料庫所取得的是參與者概括式同意(broad consent)因此，應告知事項更著重於生物資料庫本身運作機制、未來風險的告知、基因資訊對自己與家屬的影響等，也因此參與者同意書法定說明項目較其他人體研究更多，以我國的人體生物資料庫管理條例第7條規定應說明事項即有17項，超過人體研究法定應告知事項9項。其次，就參與者而言，參與生物資料庫面對的生理風險較小，但其他的風險又過於抽象遙遠，容易因此輕忽。整體而言，如何取得參與者有效的同意，完整的知情、充分的理解，應由參與者角度，檢視同意書提供的資訊是否適於理解，說明與取得同意過程，如何發展適合評估方式以參與者確認理解。現行知情同意的過程多較為單向，同意書的說明、資訊的告知較少由參與者角度思考參與生物資料庫的意義。當生物資料庫連結越來越多項目的醫療、非醫療個人資料資訊後，參與者參與將更為重要，亦即，如何確認參與者的真正理解。畢竟，知情同意作為保護參與者自主權，其要件之一即是充分理解，有必要與時俱進引入不同的作法。</p> <p> </p><p>In recent years, due to the demand for the development of precision medicine, biomedical research has been booming. Human biological databases (biobanks) based on population groups or disease patient groups can simultaneously collect biological specimens, genetic information and medical data. It saves researchers the time and cost of recruiting subjects during the research process, and can facilitate the connection of biological or medical information from different sources, so it has attracted more and more attention. In terms of ensuring the autonomy of participants in biological databases, obtaining informed consent from participants is slightly different from other human studies. The difference is that the biodatabase obtains broad consent from the participants. Therefore, the matters that should be notified focus more on the operation mechanism of the biodatabase itself, notification of future risks, and the impact of genetic information on yourself and your family members. etc. Therefore, there are more statutory explanation items in the participant consent form than in other human studies. According to Article 7 of China’s Human Biological Database Management Regulations, there are 17 items that should be explained, exceeding the 9 items that are legally required to be notified in human research. Secondly, as far as the participants are concerned, the physiological risks faced by participating in the biological database are relatively small, but other risks are too abstract and distant, so it is easy to ignore them. Overall, how to obtain effective consent, complete knowledge, and full understanding from participants should be done from the perspective of the participant, including whether the information provided in the consent form is suitable for understanding, explaining and obtaining the consent process, and how to develop appropriate evaluation methods for participation. The person confirms understanding. The current informed consent process is mostly one-way, and the explanation of the consent form and the notification of information rarely reflect the meaning of participating in the biodatabase from the perspective of the participant. As biodatabases link more and more items of medical and non-medical personal information, participant participation will become even more important, that is, how to confirm participants’ true understanding. After all, one of the requirements for informed consent, as a means of protecting participant autonomy, is a full understanding of the need to keep pace with the times and introduce different practices.</p> <p> </p>

WITHDRAWN: Impact of genetic information on Coronary Disease risk in Madeira: The GENEMACOR study

The Publisher regrets that this article is an accidental duplication of an article that has already been published, 10.1016/j.repc.2022.10.005. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Impact of genetic information on coronary disease risk in Madeira: The GENEMACOR study

IntroductionCoronary artery disease (CAD), characterized by an atherogenic process in the coronary arteries, is one of the leading causes of death in Madeira. The GENEMACOR (GENEs in MAdeira and CORonary Disease) study sought to investigate the main risk factors – environmental and genetic – and estimate whether a genetic risk score (GRS) improves CAD prediction, discrimination and reclassification. MethodsTraditional risk factors and 33 CAD genetic variants were considered in a case–control study with 3139 individuals (1723 patients and 1416 controls). The multivariate analysis assessed the likelihood of CAD. A multiplicative GRS (mGRS) was created, and two models (with and without mGRS) were prepared. Two areas under receiver operating characteristic curve (area under curve (AUC)) were analyzed and compared to discriminate CAD likelihood. Net reclassification improvement (NRI) and integrated discrimination index (IDI) were used to reclassify the population. ResultsAll traditional risk factors were strong and independent predictors of CAD, with smoking being the most significant (OR 3.25; p<0.0001). LPA rs3798220 showed a higher CAD likelihood (odds ratio 1.45; p<0.0001). Individuals in the fourth mGRS quartile had an increased CAD probability of 136% (p<0.0001). A traditional risk factor-based model estimated an AUC of 0.73, rising to 0.75 after mGRS inclusion (p<0.0001), revealing a better fit. Continuous NRI better reclassified 28.1% of the population, and categorical NRI mainly improved the reclassification of the intermediate risk group. ConclusionsCAD likelihood was influenced by traditional risk factors and genetic variants. Incorporating GRS into the traditional model improved CAD predictive capacity, discrimination and reclassification. These approaches may provide helpful diagnostic and therapeutic advances, especially in the intermediate risk group.

An actuarial model of arrhythmogenic right ventricular cardiomyopathy and life insurance

Many countries ban insurers from using genetic test results in underwriting. One study [Howard, R. C. W. (2014). Report to CIA research committee: Genetic testing model: If the underwriters had no access to known results. Canadian Institute of Actuaries (CIA).] stated that such a ban in Canada would expose life insurers to adverse selection, causing premiums to increase by 12%. More than a quarter of this cost was attributable to a single disorder, Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC). We model ARVC in a life insurance market, following the methodology of [Haçarız, O., Kleinow, T. & Macdonald, A. S. (2021). Genetics, insurance and hypertrophic cardiomyopathy. Scandinavian Actuarial Journal 2021, 54–81.], including ‘cascade’ genetic testing (CGT), so the rôle of family history in underwriting is modelled explicitly. We review (in the Appendix) the published epidemiology of ARVC, in particular the existence of an effective treatment, which we also include in our model. Our results are consistent with those of [Macdonald, A. S. & Yu, F. (2011). The impact of genetic information on the insurance industry: Conclusions from the ‘bottom-up’ modelling programme. Astin Bulletin 41(02), 343–376.] and [Haçarız, O., Kleinow, T. & Macdonald, A. S. (2021). Genetics, insurance and hypertrophic cardiomyopathy. Scandinavian Actuarial Journal 2021, 54–81.], namely, that in realistic scenarios premium increases would be negligible. We also consider the possibility of life settlement companies ‘gaming’ insurers by learning of adverse genetic test results, and conclude that to profit from purchasing policies from affected individuals, they would have to predict the future trajectory of the epidemiology of ARVC better than the epidemiologists themselves.

SY-6-1 - What should we do for better management of hereditary tumor syndromes? In the case of hereditary endocrine tumors

About 5-10％ of cancers are thought to be hereditary of which a single gene mutation is responsible for cancer development. Hereditary cancers often show different clinical courses from those of sporadic cancers. Accordingly, different clinical management can be chosen for hereditary- and sporadic cancers. Appropriate diagnosis of hereditary cancer is thus important as it enables to offer patients better and personalized management of their cancers. Also, it enables identify at-risk family members and if they have the same genetic defect as the proband, early intervention including early, and specialized surveillance and prophylactic treatment for some tumors. There are a number of hereditary endocrine tumor syndromes such as multiple endocrine neoplasia type 1 (MEN1), MEN2, von-Hippel Lindau disease, and hyperparathyroidism-jaw tumor syndrome, which manifest various endocrine- and non-endocrine tumors. Besides these, non-syndromic hereditary single tumor such as hereditary paraganglioma-pheochromocytoma syndrome, familial isolated hyperparathyroidism and familial isolated pituitary adenoma are also known. These syndromes based on the pathological germline mutation of the responsible gene and the mutation can be transmitted to the offspring. In the case of MEN2, nearly all patients develop medullary thyroid carcinoma (MTC) as early as in childhood, As about 30% of patients with MTC have MEN2 as their genetic background, all patients with MTC is strongly recommended to have genetic testing for MEN2 (RET mutation analysis). Once pathological germline mutation is detected, surgical procedure for MTC, surveillance for pheochromocytoma, and presymptomatic genetic testing for at-risk relatives are considered. In 2016, RET mutation analysis was added to the list of insurance-covered genetic testing in Japan. This will facilitate to perform testing at clinical practice which will reduce proportion of undiagnosed patients, while it could cause some complex problems related genetic counseling and family matters. All clinicians should be aware the power and impact of genetic information on clinical management and that on patients and family members.

Researching Human Genetic Variation: An Examination of the Ethics of Genetic Research

Genetic testing of whole communities is a way of picking up disease trends within that community. The diseases will not necessarily be genetically based. They will also be influenced by environmental factors. However, long-term studies hold out the hope that patterns of living combined with the genetic markers could lead to medical breakthroughs to improve the health of whole communities. The major question here is whether, once a whole community gives up the genetic material for study and analysis, they lose control over the information in that material and whether they may be harmed by the ways in which the outcomes of the research are interpreted or released. We all remember the ‘warrior gene’ news headline in New Zealand when it was suggested that a certain gene that was prevalent in Maori predisposed people to act more violently and aggressively. This had potential to deter people from wanting to release their genetic material for study. An ethical protocol is set out here so that communities are aware of how their genetic material will be used in research and are consulted about the release of the research findings before they are made public. Indigenous communities have unique concerns in relation to genetic research. The impact of genetic information on them as communities is potentially greater than the impact on other, less defined, groups. Greater assurance needs to be given that the research will be conducted in accordance with robust ethical guidelines and that it will meet their expectations. Any research relationship must respect indigenous cultural beliefs and be in keeping with their values.Researchers should explain to the community what the research is about and the potential likely findings, and how they would be released, so that the particular community can make a choice as to whether or not to be involved. Genetic samples should be considered to be ‘on loan’ to the researchers for the specific purposes for which consent was obtained. Guidelines for ethics committees in New Zealand require researchers to take steps to minimise potential harm to participants. The best way to achieve this is to work in partnership with participants to ensure that they fully understand what is happening and the researcher fully understands the participants and their potential concerns.

The Impact of Genetic Information on Policy and Clinical Practice

This article discusses genetics-related policy issues that have an impact on health care systems, health care providers, and their patients: privacy, mass screening, family screening, and knowledge dissemination. Access, cost, and ethical implications are important discussant points for each of these genetic-related policy issues. Embedded in the issue of privacy are concerns of insurability, confidentiality, and discrimination. The public health policy implications related to mass screening programs include efficacy of the screening tests, availability of primary and secondary interventions, access, costs, and program evaluation. Policy issues for family screening are similar to mass screening, with added concerns about privacy and availability of adequate resources, including health care providers and counselors trained in genetics. Knowledge dissemination is critical to maintaining currency of clinical information and applications of genetic technologies and treatments. As genetic information expands, the need for knowledge dissemination will increase. The importance of advanced practice nurses' involvement in these policy issues is discussed.