Polygenic Risk Score (PRS) Diabetes

Sony Wibisono
Surabaya Diabetes and Nutrition Centre – Division of Endocrinology and metabolism –Department of
Internal Medicine – dr Soetomo Teaching Hospital - Faculty of Medicine – Airlangga University
Bima, 20 May 2023
Outline
• The global increase diabetes prevalence, as a significant global
challenge to the health and well-being of people
• Diabetes and glycemic trait associated variants
• Polygenic Risk Score diabetes
• DIARisk
DM dan komplikasinya : penyakit metabolik dengan morbiditas tinggi
DM dan komplikasinya : penyakit metabolik dengan morbiditas tinggi
Genes, diet and type 2 diabetes mellitus :
Disease-related Phenotypes

http://dx.doi.org/10.1900/RDS.2007.3.13
The Type 1 Diabetes (T1D) Susceptibility Loci
A Polygenic Score for Type 2 Diabetes Improves Risk Stratification Beyond Current Clinical
Screening Factors in an Ancestrally Diverse Sample
https://doi.org/10.1186/s40246-021-00339-y
 How polygenic scores are derived. The orange dashed line in the graph represents the threshold for ...

Endocr Rev, Volume 40, Issue 6, December 2019, Pages 1500–1520, https://doi.org/10.1210/er.2019-00088
The content of this slide may be subject to copyright: please see the slide notes for details.
https://doi.org/10.1210/er.2019-00088
Partitioned Polygenic Score Clusters Capturing Etiological Heterogeneity in T2D Comparison of pPS clusters identified by
Mahajan et al. (20) and Udler et al. (38).Abbreviations: TG, triglyceride; WHR, waist/hip ratio.
Cluster Name
Physiological Impact Phenotypic Features
Udler et al., 2018 (38) Mahajan et al., 2018 (20) Examples of T2D Loci

Adverse impact on β-cell High proinsulin Low fasting insulin (+ β-Cell Insulin secretion 1 ABO, ADCY5, HNF1A, H
function high proinsulin) NF1B, MTNR1B, SLC30A
8, TCF7L2

Low proinsulin Low fasting insulin (+ Proinsulin Insulin secretion 2 IGF2BP2, CENTD2/
low proinsulin) ARAP1, CCND2

Reduced insulin Mediation with fat High fasting insulin + low Lipodystrophy Insulin action MACF1, GRB14, IRS1, P
sensitivity distribution BMI + low WC + high PARG, ANKRD55, KLF14
TG , LPL, CMIP

Mediation via obesity High fasting insulin + Obesity Adiposity NRXN3, FTO, MC4R
high BMI + high WC

Mediation via lipid Low TG Liver/lipid Dyslipidemia GCKR, TM6SF2

metabolism

Undetermined No striking phenotype No assignment Mixed features BCL11A, TLE1, PLEKHA

association 1, HMGA2, MTMR3

https://doi.org/10.1210/er.2019-00088
https://doi.org/10.3390/jpm11060582
https://doi.org/10.1007/s00125-021-05491-7
Clustering of combined macrovascular disease risk by multiPRS using
unsupervised hierarchical clustering algorithm
Contribution of genomic and non-genomic factors to the risk prediction model
Frequency of major microvascular and macrovascular events by genomic (10wPRS + PC1) and
age at onset of diabetes strata
Polygenic risk scores predict diabetes complications and their response to intensive blood pressure and glucose control
 GWAS study result

Suatu SNP dikatakan terkait dengan penyakit jika tingkat signifikansi 10-8
 Genomic Risk Prediction
HUMAN GENOME STUDY

The Odds Ratio (OR value)

Mengukur tingkat pengaruh, dan tingkat asosiasi. Secara khusus, OR juga digunakan untuk
memberikan informasi mengenai keterkaitan antara alel dengan penyakit

OR T = 1
Tidak ada asosiasi antara genotip dengan penyakit
OR T > 1
Adanya asosiasi alel T dengan penyakit

OR T < 1
T alel memiliki sifat protektif
 Newer studies based on hundreds of
thousands of people and millions of genetic
variants indicate that genetic risk scores can
now outperform traditional risk factors in risk
prediction.

Knowles JW & Ashley EA. 2018. PLoS Med 15(3):e1002546.

Dainis AM & Ashley EA. 2018. JACC:

Basic Transl Sci 3(2): 313-326.
 Cho Y, Lee J, Park K, Nho C. Genetics of Type 2 Diabetes in East Asian Populations. Current Diabetes Reports. 2012;12(6):686-696.

Beberapa gen/varian pada populasi Asia tidak

dapat ditemukan di populasi Eropa begitupan sebaliknya
Itulah sebabnya Prodia menggunakan ASA
DIArisk result
DIARisk

• Berusia 18 tahun sampai dengan 30 tahun,

• Bertujuan kepada intervensi strategi pencegahan dini diabetes
• DIArisk dapat menjadi pilihan masyarakat dalam melakukan tindakan
preventif terhadap risiko penyakit diabetes dan komplikasinya.
• DIArisk hanya diperiksa satu kali seumur hidup.
• DIArisk berguna untuk menilai risiko penyakit berdasarkan profil
genetik.
DIARisk

• Pemeriksaan genomik pertama di indonesia yang melihat risiko

diabetes dan penyakit terkait diabetes.
• Berbasis gen yang menganalisis kurang lebih 100 gen dan varian untuk
mengetahui faktor risiko diabetes dan penyakit terkait diabetes.
• Jenis diabetes tipe 1, diabetes tipe 2 dan gestational diabetes
• Komplikasinya adalah neuropati diabetes dan nefropati diabetes.
• Faktor risiko obesitas, kelainan metabolisme lipid, dan penyakit ginjal
kronis
• Bukan bertujuan untuk mendiagnosis seseorang menderita diabetes
 Surabaya Diabetes and Nutrition Centre – dr Soetomo Hospital – Faculty of Medicine – Airlangga
University

THANK YOU
 Genetic and environmental
factors affecting islet function
and connecting obesity and
T2DM

https://doi.org/10.3389/fendo.2023.1161521
 The critical roles of obesity-
induced insulin resistance in the
consequent pathogenesis of T2DM

https://doi.org/10.3389/fendo.2023.1161521
 Mechanisms of fatty acids
affecting insulin signaling and
fueling hyperglycemia

https://doi.org/10.3389/fendo.2023.1161521
 Regulators of the
microbiome-gut-brain axis

https://doi.org/10.3389/fendo.2023.1161521
https://doi.org/10.3389/fendo.2023.1161521