On the utilization of polygenic risk scores for therapeutic targeting.

On the utilization of polygenic risk scores for therapeutic targeting.

Publication date: Apr 01, 2019

The promise of personalized genomic medicine is that knowledge of a person’s gene sequences and activity will facilitate more appropriate medical interventions, particularly drug prescriptions, to reduce the burden of disease. Early successes in oncology and pediatrics have affirmed the power of positive diagnosis and are mostly based on detection of one or a few mutations that drive the specific pathology. However, genetically more complex diseases require the development of polygenic risk scores (PRSs) that have variable accuracy. The rarity of events often means that they have necessarily low precision: many called positives are actually not at risk, and only a fraction of cases are prevented by targeted therapy. In some situations, negative prediction may better define the population at low risk. Here, I review five conditions across a broad spectrum of chronic disease (opioid pain medication, hypertension, type 2 diabetes, major depression, and osteoporotic bone fracture), considering in each case how genetic prediction might be used to target drug prescription. This leads to a call for more research designed to evaluate genetic likelihood of response to therapy and a call for evaluation of PRS, not just in terms of sensitivity and specificity but also with respect to potential clinical efficacy.

Open Access PDF

Gibson, G. On the utilization of polygenic risk scores for therapeutic targeting. 04469. 2019 PLoS Genet (15):4.

Concepts Keywords
Bone Fracture Therapy
Depression Depression
Diabetes Major depressive disorder
Genetic Medical prescription
Hypertension Bipolar spectrum
Opioid RTT
Osteoporotic Articles
Pain Medication Psychiatric diagnosis
Pathology Health
Pediatrics Drug prescriptions
Polygenic Drug prescription
Spectrum
Targeted Therapy

Semantics

Type Source Name
drug DRUGBANK Coenzyme M
gene UNIPROT BRD2
gene UNIPROT PLXNA2
disease MESH Comas
gene UNIPROT PRAC1
gene UNIPROT POLG
gene UNIPROT TWNK
disease MESH drug interactions
drug DRUGBANK Polyethylene glycol
gene UNIPROT PLEKHG5
drug DRUGBANK Cholesterol
disease DOID heart disease
disease MESH heart disease
gene UNIPROT BEST1
gene UNIPROT DMD
disease DOID osteoporosis
disease MESH osteoporosis
gene UNIPROT FBLIM1
drug DRUGBANK Romosozumab
drug DRUGBANK Alendronic acid
drug DRUGBANK Progesterone
gene UNIPROT CYP2C19
gene UNIPROT COL17A1
disease MESH heterozygote
gene UNIPROT SAFB
gene UNIPROT SLC22A18
gene UNIPROT HTR2A
drug DRUGBANK Serotonin
gene UNIPROT ADM
disease MESH neuroticism
disease MESH depressive disorder
gene UNIPROT LIF
gene UNIPROT DIAPH2
disease MESH syndrome
disease DOID syndrome
disease MESH weight reduction
gene UNIPROT ST13
gene UNIPROT RPL29
gene UNIPROT REG3A
gene UNIPROT HHIP
gene UNIPROT FBN1
gene UNIPROT DSPP
gene UNIPROT SLC5A2
drug DRUGBANK Exenatide
disease MESH infarction
disease DOID stroke
disease MESH stroke
gene UNIPROT EHMT1
gene UNIPROT RCBTB1
gene UNIPROT GOLGA6A
gene UNIPROT ARNTL
gene UNIPROT PSD4
disease DOID hyperglycemia
disease MESH tic
disease MESH hyperglycemia
pathway BSID Insulin secretion
gene UNIPROT EHD1
disease MESH multiple
gene UNIPROT OPRM1
pathway BSID Gluconeogenesis
drug DRUGBANK D-glucose
drug DRUGBANK Dextrose unspecified form
drug DRUGBANK Metformin
gene UNIPROT MENT
drug DRUGBANK Trestolone
gene UNIPROT MAGEE1
gene UNIPROT ELL
disease MESH men
gene UNIPROT RNMT
gene UNIPROT SLTM
gene UNIPROT MET
drug DRUGBANK Methionine
gene UNIPROT TRIM13
gene UNIPROT CXADR
gene UNIPROT NR1I3
gene UNIPROT CASR
gene UNIPROT PRKAR1A
gene UNIPROT SPG7
disease MESH hypotension
disease MESH syncope
drug DRUGBANK Hyaluronic acid
gene UNIPROT CAD
gene UNIPROT DFFB
gene UNIPROT KIDINS220
gene UNIPROT ACOD1
gene UNIPROT SMIM10L2A
gene UNIPROT SMIM10L2B
disease MESH heart failure
disease MESH overweight
drug DRUGBANK Acetohydroxamic acid
disease MESH death
gene UNIPROT JTB
gene UNIPROT NR1I2
drug DRUGBANK Calcium
gene UNIPROT ACE
drug DRUGBANK Angiotensin II
disease MESH diuretic
disease MESH life style
gene UNIPROT CCHCR1
gene UNIPROT SHBG
gene UNIPROT DNMT1
gene UNIPROT CD5L
gene UNIPROT CD69
disease DOID ers
gene UNIPROT NAA50
drug DRUGBANK Hydrocodone
drug DRUGBANK Oxycodone
drug DRUGBANK Tramadol
drug DRUGBANK Codeine
gene UNIPROT CYP2D6
gene UNIPROT CYP2D7
gene UNIPROT LARGE1
disease DOID constipation
disease MESH respiratory depression
drug DRUGBANK Morphine
gene UNIPROT COPE
gene UNIPROT BAD
drug DRUGBANK Diamorphine
gene UNIPROT SSRP1
drug DRUGBANK Fentanyl
gene UNIPROT DNER
gene UNIPROT ARSA
gene UNIPROT THOP1
drug DRUGBANK Acetylsalicylic acid
gene UNIPROT DEPP1
gene UNIPROT GOPC
gene UNIPROT NNT
gene UNIPROT TECR
gene UNIPROT ORC3
gene UNIPROT LAT
gene UNIPROT SPNS1
gene UNIPROT TNFSF13
gene UNIPROT ANP32B
gene UNIPROT ATM
disease MESH breast cancer
disease DOID breast cancer
pathway BSID Breast cancer
disease DOID atrial fibrillation
disease MESH atrial fibrillation
disease DOID coronary artery disease
disease MESH coronary artery disease
gene UNIPROT MS4A2
gene UNIPROT PHF11
gene UNIPROT CHL1
disease MESH type 2 diabetes
disease MESH depression
disease DOID hypertension
disease MESH hypertension
disease MESH chronic disease
drug DRUGBANK Tropicamide
disease MESH development
disease MESH diagnosis
gene UNIPROT RBM12
gene UNIPROT INTU
disease MESH estrogen
gene UNIPROT PKHD1
disease MESH osteoporotic fractures
drug DRUGBANK Ferric pyrophosphate citrate
gene UNIPROT CHPT1
gene UNIPROT DHDDS
gene UNIPROT EAF2
gene UNIPROT ALX4
gene UNIPROT DUOXA1
disease DOID major depressive disorder
disease MESH major depressive disorder
gene UNIPROT APP
disease MESH community
gene UNIPROT COX5A
gene UNIPROT COX8A
gene UNIPROT CPOX
gene UNIPROT AGAP2
disease MESH Coronary Heart Disease
gene UNIPROT CD36
gene UNIPROT FAT1
drug DRUGBANK Palmitic Acid
gene UNIPROT SOX10
drug DRUGBANK Semaglutide
drug DRUGBANK Liraglutide
drug DRUGBANK Rasagiline
gene UNIPROT CMC2
gene UNIPROT YES1
disease MESH risk factor
disease MESH complications
gene UNIPROT EXOG
gene UNIPROT KCNJ5
gene UNIPROT PCNA
gene UNIPROT CIR1
gene UNIPROT BAMBI
gene UNIPROT GRB2
gene UNIPROT ABCB6
gene UNIPROT JAG1
drug DRUGBANK Abacavir
gene UNIPROT BMS1
gene UNIPROT ACACA
gene UNIPROT SLC26A5
gene UNIPROT F11R
gene UNIPROT WLS
gene UNIPROT COMP
gene UNIPROT COL9A3
gene UNIPROT COL9A1
gene UNIPROT COL9A2
gene UNIPROT SOAT1
gene UNIPROT SCN8A
gene UNIPROT AIFM2

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