Implementation of genomics in medical practice to deliver precision medicine for an Asian population

Abstract

Whilst the underlying principles of precision medicine are comparable across the globe, genomic references, health practices, costs and discrimination policies differ in Asian settings compared to the reported initiatives involving European-derived populations. We have addressed these variables by developing an evolving reference base of genomic and phenotypic data and a framework to return medically significant variants to consenting research participants applicable for the Asian context. Targeting 10,000 participants, over 2000 Singaporeans, with no known pre-existing health conditions, have consented to an extensive clinical health screen, family health history collection, genome sequencing and ongoing follow-up. Genomic variants in a subset of genes associated with Mendelian disorders and drug responses are analysed using an in-house bioinformatics pipeline. A multidisciplinary team reviews the classification of variants and a research report is generated. Medically significant variants are returned to consenting participants through a bespoke return-of-result genomics clinic. Variant validation and subsequent clinical referral are advised as appropriate. The design and implementation of this flexible learning framework enables a cohort of detailed phenotyping and genotyping of healthy Singaporeans to be established and the frequency of disease-causing variants in this population to be determined. Our findings will contribute to international precision medicine initiatives, bridging gaps with ethnic-specific data and insights from this understudied population.

Family History Assessment Significantly Enhances Delivery of Precision Medicine in the Genomics Era

“…Details of participant recruitment and methods of both Biobank and SingHeart have been previously described. 15 Briefly, volunteers with no known preexisting health conditions over 16 years of age were recruited in response to a research advertisement in the local paper in 2014. They consented to a detailed medical screen and a genetic screen using whole genome sequencing technology.…”

“…Data was returned in the form of FASTQ files and analysed using an in-house bioinformatics pipeline as previously described. 15 Variants occurring in the customised cancer gene panel were filtered by frequency against a populationmatched database and selected according to their classification for both exonic and intronic regions in ClinVar 23 or disruption to protein function and curated according to ACMG guidelines 24 .…”

Practical Aspects in Genetic Testing for Cardiomyopathies and Channelopathies

“…Incomplete penetrance in cardiac disorders might imply a larger proportion of asymptomatic carriers to be detected on cascade testing and a more significant issue of genetic discrimination and stigmatisation, especially when genetic non-discrimination regulations have not been implemented in many countries. 120 The Australian Genetic Discrimination Project revealed a concerning number of cases of alleged genetic discrimination in terms of negative treatment in insurance and health as well as employment domains. 121 In no circumstance should family members be coerced into testing, and the issues of potential genetic discrimination in health insurance and employment might well prohibit patients from participating in cascade testing.…”

"Who is Watching the Watchdog?": Ethical Perspectives of Sharing Health-related Data for Precision Medicine in Singapore

“…12 Some of this data has been linked to patients' electronic medical records (EMR) and used to support clinical care under the SingHealth Duke-NUS Institute of PRecISion Medicine (PRISM) initiative. 13 Singapore has the capacity to upscale this initiative across the public healthcare system, which is served by a national IT provider that can integrate health information from multiple sources, including EMR, biobanks and administrative databases. 14 This combination of comprehensive health information, and expertise in genomics research and clinical implementation, 15 puts Singapore in a strong position to initiate a nation-wide PM programmes and contribute to similar initiatives internationally.…”