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

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

Publication date: Jun 08, 2019

With an initial target of 10,000 volunteers, aged 18 years and above, to date over 2000 participants with no known pre-existing health conditions have consented to undergo a detailed health screen, collection of family health history (FHH) and lifestyle activity information and a genetic screen using whole genome sequencing technology.

As such, the PRISM institute was purpose-built to include a research facility to correlate genomic and clinical data using bioinformatics analytics and a clinical facility comprising of genetic counselling, medical examination and clinical consultation rooms.

Participants are informed that only genes associated with clinical actionability will be reviewed and could indicate: Participants are informed that a genetic counsellor is available during the recruitment appointment to aid in the decision regarding the option to receive genomic findings.

To avoid any confusion, training and handouts were provided to the clinical research coordinators to assist the collection of relevant family history and it is explained to the participants that information from only blood-related family members is relevant.

The additional genes considered for analysis are based on the reported experience of international genomics experts and the local experience of genetic conditions found prevalent in Southeast Asian populations.

Additionally, our SEC local genomic database is analysed to understand carrier prevalence of genetic conditions that are more common in the local population, including diseases such as thalassaemia (1 in 25), citrin deficiency (1 in 41) and Wilson disease (1 in 103). 8,14,15,16,17,18 The ACMG framework was used as a guide for assessing the clinical actionability of genes in our panel. 19 Subsequently, the screening recommendations for each associated genetic condition were then reviewed to ensure that a management plan for ongoing follow-up could be offered in the Singapore context.

Additionally, six genes (KCNE3, CACNA1C, CACNB2, GPD1L, HCN4, SCN3B) were removed from the PRISM gene list because the disease association with Brugada syndrome was classified as -Disputed” in ClinGen. 20 In addition, there is limited evidence for the association of HCN4 with familial thoracic aortic aneurysm and aortic dissection, and no reported evidence for the association of CACNB2 with hypertrophic cardiomyopathy. 21 The PRISM gene list version 2 contains 115 genes associated with Mendelian disorders and 22 pharmacogenomic genes (further details in Supplementary text).

Of these variants, information in accordance with the ACMG variant classification guidelines23 is prepared and presented at a monthly multidisciplinary team (MDT) meeting comprising of clinical genetics, research and bioinformatics experts and critically reviewed.

For these variants, which are classified as variants of unknown significance (VUS), if additional information such as further FHH or a routine clinical laboratory test to ascertain the phenotype, such as a lipid profile, will assist with the interpretation, then these participants are also recontacted.

Concepts Keywords
Aortic Dissection Pharmacogenomic
APOB Pharmacogenomics
Asian Whole genome sequencing
Autosomal Dominant Genetic counseling
Autosomal Recessive PharmGKB
Bioinformatic Cancer research
Blood Biological databases
Brugada Syndrome Medical genetics
Clinical Geneticist Genomics
Clinical Genetics Genetics
Clinical Laboratory Branches of biology
Congenital Adrenal Hyperplasia Counselling
CYP21A2 Thoracic aortic aneurysm
Familial Hypercholesterolemia Diseases
Frameshift Congenital adrenal hyperplasia
Frequency Citrin deficiency
Genetic Hospital services
Genetic Condition
Genetic Counselling
Genetic Counsellor
Genetic Screen
Genome
Gold Standard
Hospital
Hypertrophic Cardiomyopathy
Illumina
Kinship System
Logistics
MDT
Mendelian
Mendelian Disorders
Mutation
Pathogenic
Pathogenicity
Pharmacogenomic
Phenotype
Pipeline
PRISM
Pseudogene
Questionnaire
SEC
Sequencing
Singapore
Socioeconomic
Splice Site
Thalassaemia

Semantics

Type Source Name
disease MESH family health history
disease DOID FHH
gene UNIPROT CASR
disease MESH lifestyle
gene UNIPROT PRDM6
gene UNIPROT GOPC
gene UNIPROT DEPP1
gene UNIPROT AICDA
disease MESH community
disease MESH confusion
disease MESH multiple
disease MESH citrin deficiency
disease DOID Wilson disease
disease MESH familial hypercholesterolemia
disease DOID familial hypercholesterolemia
gene UNIPROT APOB
gene UNIPROT LDLRAP1
gene UNIPROT PCSK9
gene UNIPROT CYP21A2
disease MESH congenital adrenal hyperplasia
disease DOID congenital adrenal hyperplasia
gene UNIPROT KCNE3
gene UNIPROT CACNA1C
gene UNIPROT CACNB2
gene UNIPROT GPD1L
gene UNIPROT HCN4
gene UNIPROT SCN3B
disease MESH Brugada syndrome
disease DOID Brugada syndrome
disease MESH hypertrophic cardiomyopathy
disease DOID hypertrophic cardiomyopathy
gene UNIPROT BEST1
gene UNIPROT KIT
gene UNIPROT MAP6
gene UNIPROT SMC3
gene UNIPROT BCL2L11
drug DRUGBANK Gold

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