Turkiye Klinikleri Journal of Biostatistics

.: ORIGINAL RESEARCH
Prediction of Polygenic Risk Score by Machine Learning and Deep Learning Methods in Genome-wide Association Studies: Methodological Study
Genom-boyu İlişki Çalışmalarında Poligenik Risk Skorunun Makine Öğrenimi ve Derin Öğrenme Yöntemleri ile Tahmin Edilmesi: Metodolojik Çalışma
Ragıp Onur ÖZTORNACIa , Erdal COŞGUNb , Cemil ÇOLAKc , Bahar TAŞDELENd
aUniversity of Bristol, Department of Population Health Sciences, The MRC Integrative Epidemiology Unit, Bristol, UK
bMicrosoft Research, USA
cİnönü University Faculty of Medicine, Department of Biostatistics, Malatya, Türkiye
dMersin University Faculty of Medicine, Department of Biostatistics, Mersin, Türkiye
Turkiye Klinikleri J Biostat. 2025;17(1):28-39
doi: 10.5336/biostatic.2025-108361
Article Language: EN
Full Text
ABSTRACT
 Objective: We aimed to investigate whether machine learning (ML) and deep learning (DL) methods, utilizing individual-level data from genome-wide association studies (GWAS), could serve as a viable alternative to traditional polygenic risk score (PRS) calculation methods, which rely on odds ratios as weights. PRS is widely used to estimate genetic susceptibility to diseases, but its accuracy and generalizability can be affected by variations in allele frequencies and sample sizes. Given the advancements in ML and DL techniques, we explored their potential for improving risk prediction. Material and Methods: We generated GWAS datasets using the PLINK program, simulating genetic data under various conditions by varying allele frequencies and sample sizes. This process was repeated 100 times to assess the robustness of the approaches. We applied 2 ML algorithms-Support Vector Machine and Random Forest alongside a DL approach. The predictive performance of these methods was compared to the traditional PRS calculation, which uses odds ratios as weights. Results: Our findings showed that ML and DL methods provided more consistent case-control separation than the classical approach. Additionally, they exhibited reduced bias and greater stability across different genetic conditions. Conclusion: ML and DL approaches present a promising alternative to odds ratio-based PRS calculations, offering enhanced reliability and consistency in genetic risk prediction.

Keywords: Genome-wide association studies; polygenic risk score; deep learning; machine learning; precision medicine
ÖZET
 Amaç: Bu çalışmada, genom-boyu ilişkilendirme çalışması [genome-wide association studies (GWAS)] verilerinden elde edilen bireysel düzey bilgileri kullanarak, poligenik risk skoru (PRS) hesaplamasında, olasılık oranlarını ağırlık olarak kullanan geleneksel yaklaşımlara alternatif olarak, makine öğrenimi [machine learning (ML)] ve derin öğrenme [deep learning (DL)] yöntemlerinin uygulanabilirliğini araştırmayı amaçladık. PRS, hastalıklara genetik yatkınlığın tahmininde yaygın olarak kullanılmaktadır; ancak, alel frekanslarındaki ve örneklem büyüklüklerindeki farklılıklar nedeniyle doğruluğu ve genellenebilirliği etkilenebilmektedir. Son yıllarda ML ve DL tekniklerindeki ilerlemeler göz önüne alındığında, bu yöntemlerin risk tahminini iyileştirip iyileştiremeyeceğini değerlendirdik. Gereç ve Yöntemler: PLINK programı kullanılarak farklı alel frekansları ve örneklem büyüklüklerinde 100 kez tekrarlanan GWAS veri setleri oluşturuldu. Ardından, bu veri setleri üzerinde 2 farklı ML algoritması (Destek Vektör Makinesi ve Rastgele orman) ile bir DL yaklaşımı uygulandı. Bu yöntemlerin performansı, olasılık oranlarını ağırlık olarak kullanan klasik PRS hesaplama yöntemiyle karşılaştırıldı. Bulgular: ML ve DL yaklaşımları, klasik yönteme kıyasla vaka-kontrol ayrımında daha tutarlı sonuçlar üretti. Ayrıca, farklı alel frekansları ve örneklem büyüklükleri altında daha az yanlılık ve daha yüksek kararlılık sergiledikleri gözlendi. Sonuç: ML ve DL tabanlı yöntemler, PRS hesaplamasında geleneksel olasılık oranına dayalı yaklaşımlara kıyasla daha güvenilir ve tutarlı bir risk tahmini sunarak alternatif bir yöntem olarak öne çıkmaktadır.

Anahtar Kelimeler: Genom-boyu ilişki çalışmaları; poligenik risk skoru; derin öğrenme; makine öğrenimi; hassas tıp
REFERENCES:
  1. Dorak MT. Genetic Association Studies: Background, Conduct, Analysis, and Interpretation. 1st ed. New York: Garland Science; 2016. [Crossref] 
  2. Konuma T, Okada Y. Statistical genetics and polygenic risk score for precision medicine. Inflamm Regen. 2021;41(1):18. [Crossref]  [PubMed]  [PMC] 
  3. Choi SW, Mak TS, O?Reilly PF. Tutorial: a guide to performing polygenic risk score analyses. Nat Protoc. 2020;15(9):2759-72. [Crossref]  [PubMed]  [PMC] 
  4. Alpaydın E. Introduction to Machine Learning. 3rd ed. Cambridge: The MIT Press; 2004. [Crossref] 
  5. Akpınar H. Data Veri Madenciliği Veri Analizi. 1. Baskı. İstanbul: Papatya Yayıncılık; 2013
  6. Gönen M, Alpaydın E. Multiple kernel learning algorithms. Journal of Machine Learning Research. 2011;12:2211-68. [Link] 
  7. Köse T, Özgür S, Coşgun E, Keskinoğlu A, Keskinoğlu P. Effect of missing data imputation on deep learning prediction performance for vesicoureteral reflux and recurrent urinary tract infection clinical study. Biomed Res Int. 2020;2020:1895076. [Crossref]  [PubMed]  [PMC] 
  8. Han J, Kamber M, Pei J. Data Mining: Concepts and Techniques. The Morgan Kaufmann Series in Data Management Systems. 3rd ed. San Francisco: Elsevier; 2012.
  9. Pisner DA, Schnyer DM. Support vector machine. Machine Learning. 2020:101-21. DOI: [Crossref] 
  10. Biau G, Scornet E. A random forest guided tour. TEST. 2016;25:197-227. [Crossref] 
  11. Orekici Temel G, Camdeviren H, Akkus Z. Diagnosing restless legs syndrome (RLS) patients with help of classification tree. Annals of Medical Research. 2021;12(2):111-7. [Link] 
  12. Strobl C, Zeileis A. Danger: High power!-exploring the statistical properties of a test for random forest variable importance. In Brito P, eds. COMPSTAT 2008-Proceedings in Computational Statistics, Vol. II. Heidelberg: Physica-Verlag; 2008. p. 59-66. [Crossref] 
  13. Liu Y, Zhao H. Variable importance-weighted Random Forests. Quant Biol. 2017;5(4):338-51. [PubMed]  [PMC] 
  14. Aminanto ME, Kim K. Deep Learning in Intrusion Detection Systems: An Overview. Proceedings of the 2016 International Research Conference on Engineering and Technology; 2016 March 17-18; Hong Kong: 2016. p.1-12. [Link] 
  15. Cho K, van Merriënboer B, Gulcehre C, Bahdanau D, Bougares F, Schwenk H, et al. Learning phrase representations using RNN encoder-decoder for statistical machine translation. Proceedings of the 2014 Conference on Empirical Methods in Natural Language Processing (EMNLP). 2014:1724-34. [Crossref] 
  16. Luong MT, Pham H, Manning CD. Effective approaches to attention-based neural machine translation. Proceedings of the 2015 Conference on Empirical Methods in Natural Language Processing. 2015:1412-21. [Crossref] 
  17. Hecht-Nielsen R. Theory of the Backpropagation Neural Network. Neural Networks for Perception Computation, Learning, and Architectures. 1992:65-93. [Crossref] 
  18. Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D. Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet. 2006;38(8):904-9. [Crossref]  [PubMed] 
  19. Zollner S, Pritchard JK. Overcoming the winner?s curse: estimating penetrance parameters from case-control data. Am J Hum Genet. 2007;80(4):605-15. [Crossref]  [PubMed]  [PMC] 
  20. Sebastiani P, Timofeev N, Dworkis DA, Perls TT, Steinberg MH. Genome-wide association studies and the genetic dissection of complex traits. Am J Hematol. 2009;84(8):504-15. [PubMed]  [PMC] 
  21. Bush WS, Moore JH. Chapter 11: Genome-wide association studies. PLoS Comput Biol. 2012;8(12):e1002822. [Crossref]  [PubMed]  [PMC] 
  22. Storey JD, Tibshirani R. Statistical significance for genomewide studies. Proc Natl Acad Sci U S A. 2003;100(16):9440-5. [Crossref]  [PubMed]  [PMC] 
  23. Thomas DC, Conti DV. Commentary: the concept of ?Mendelian Randomization?. Int J Epidemiol. 2004;33(1):21-5. [PubMed] 
  24. Voight BF, Pritchard JK. Confounding from cryptic relatedness in case-control association studies. PLoS Genet. 2005;1(3):e32. [Crossref]  [PubMed]  [PMC] 
  25. R Core Team. R language definition. Vienna, Austria: R Foundation for Statistical Computing; 2000.
  26. Copeland M, Soh J, Puca A, Manning M, Gollob D. Microsoft Azure: Planning, Deploying, and Managing Your Data Center in the Cloud. 1st ed. New York, USA: Apress; 2015. p. 3-26. [Crossref] 
  27. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81(3):559-75. [Crossref]  [PubMed]  [PMC] 
  28. Sobell MG. A practical guide to Ubuntu Linux. 4th ed. Canada; Pearson Education: 2015.
  29. Black MH, Li S, LaDuca H, Lo MT, Chen J, Hoiness R, et al. Validation of a prostate cancer polygenic risk score. Prostate. 2020;80(15):1314-21. [Crossref]  [PubMed]  [PMC] 
  30. Elliott J, Bodinier B, Bond TA, Chadeau-Hyam M, Evangelou E, Moons KGM, et al. Predictive Accuracy of a Polygenic Risk Score-Enhanced Prediction Model vs a Clinical Risk Score for Coronary Artery Disease. JAMA. 2020;323(7):636-45. [Crossref]  [PubMed]  [PMC] 
  31. Placek K, Benatar M, Wuu J, Rampersaud E, Hennessy L, Van Deerlin VM, et al; CReATe Consortium; Chen W, Wu G, Paul Taylor J, McMillan CT. Machine learning suggests polygenic risk for cognitive dysfunction in amyotrophic lateral sclerosis. EMBO Mol Med. 2021;13(1):e12595. [Crossref]  [PubMed]  [PMC] 
  32. Huang S, Ji X, Cho M, Joo J, Moore J. DL-PRS: a novel deep learning approach to polygenic risk scores. Research Square. 2021. [Crossref] 
  33. Mamani NM. Applications of machine learning techniques and polygenic risk scores to genetic disease prediction. ADCAIJ: Advances in Distributed Computing and Artificial Intelligence Journal. 2020;9(1):5-14. [Crossref] 
  34. Paré G, Mao S, Deng WQ. A machine-learning heuristic to improve gene score prediction of polygenic traits. Scientific Reports. 2017;7(1):1-11. [Crossref] 

.: Up To Date

.: Process List

Login

 Forgot your password?

 New Registration  

Contact

Ortadoğu Reklam Tanıtım Yayıncılık Turizm Eğitim İnşaat Sanayi ve Ticaret A.Ş.

.: Address

Turkocagi Caddesi No:30 06520 Balgat / ANKARA
Phone: +90 312 286 56 56
Fax: +90 312 220 04 70
E-mail: info@turkiyeklinikleri.com

.: Manuscript Editing Department

Phone: +90 312 286 56 56/ 154 - 153
E-mail: yaziisleri@turkiyeklinikleri.com

.: English Language Redaction

Phone: +90 312 286 56 56/ 145
E-mail: tkyayindestek@turkiyeklinikleri.com

.: Marketing Sales-Project Department

Phone: +90 312 286 56 56/ 142
E-mail: reklam@turkiyeklinikleri.com

.: Subscription and Public Relations Department

Phone: +90 312 286 56 56/ 197
E-mail: abone@turkiyeklinikleri.com

.: Customer Services

Phone: +90 312 286 56 56/ 197
E-mail: satisdestek@turkiyeklinikleri.com

1. TERMS OF USE

1.1. To use the web pages with http://www.turkiyeklinikleri.com domain name or the websites reached through the sub domain names attached to the domain name (They will be collectively referred as "SITE"), please read the conditions below. If you do not accept these terms, please cease to use the "SITE." "SITE" owner reserves the right to change the information on the website, forms, contents, the "SITE," "SITE" terms of use anytime they want.

1.2. The owner of the "SITE" is Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. (From now on it is going to be referred as "Turkiye Klinikleri", shortly) and it resides at Turkocagi cad. No:30, 06520 Balgat Ankara. The services in the "SITE" are provided by "Turkiye Klinikleri."

1.3. Anyone accessing the "SITE" with or without a fee whether they are a natural person or a legal identity is considered to agree these terms of use. In this contract hereby, "Turkiye Klinikleri" may change the stated terms anytime. These changes will be published in the "SITE" periodically and they will be valid when they are published. Any natural person or legal identity benefiting from and reaching to the "SITE" are considered to be agreed to any change on hereby contract terms done by "Turkiye Klinikleri."

1.4. The "Terms of Use" hereby is published in the website with the last change on March 30th 2014 and the "SITE" is activated by enabling the access to everyone. The "Terms of Use" hereby is also a part of the any "USER Contract" was and/or will be done with the users using "Turkiye Klinikleri" services with or without a fee an inseparable.

2. DEFINITIONS

2.1. "SITE": A website offering different kind of services and context with a certain frame determined by "Turkiye Klinikleri" and it is accessible on-line on http://www.turkiyeklinikleri.com domain name and/or subdomains connected to the domain name.

2.2. USER: A natural person or a legal identity accessing to the "SITE" through online settings.

2.3. LINK: A link enabling to access to another website through the "SITE", the files, the context or through another website to the "SITE", the files and the context.

2.4. CONTEXT: Any visual, literary and auditory images published in the "Turkiye Klinikleri", "SITE" and/or any website or any accessible information, file, picture, number/figures, price, etc.

2.5. "USER CONTRACT": An electronically signed contract between a natural or a legal identity benefiting from special services "Turkiye Klinikleri" will provide and "Turkiye Klinikleri".

3. SCOPE OF THE SERVICES

3.1. "Turkiye Klinikleri" is completely free to determine the scope and quality of the services via the "SITE".

3.2. To benefit the services of "Turkiye Klinikleri" "SITE", the "USER" must deliver the features that will be specified by "Turkiye Klinikleri". "Turkiye Klinikleri" may change this necessity any time single-sided.

3.3. Not for a limited number, the services "Turkiye Klinikleri" will provide through the "SITE" for a certain price or for free are;

- Providing scientific articles, books and informative publications for health industry.

- Providing structural, statistical and editorial support to article preparation stage for scientific journals.

4. GENERAL PROVISIONS

4.1. "Turkiye Klinikleri" is completely free to determine which of the services and contents provided in the "SITE" will be charged.

4.2. People benefiting from the services provided by "Turkiye Klinikleri" and using the website can use the "SITE" only according to the law and only for personal reasons. Users have the criminal and civil liability for every process and action they take in the "SITE". Every USER agrees, declares and undertakes that they will not proceed by any function or action infringement of rights of "Turkiye Klinikleri"s and/or other third parties', they are the exclusive right holder on usage, processing, storage, made public and revealing any written, visual or auditory information reported to Turkiye Klinikleri" and/or "SITE" to the third parties. "USER" agrees and undertakes that s/he will not duplicate, copy, distribute, process, the pictures, text, visual and auditory images, video clips, files, databases, catalogs and lists within the "SITE", s/he will not be using these actions or with other ways to compete with "Turkiye Klinikleri", directly or indirectly.

4.3. The services provided and the context published within the "SITE" by third parties is not under the responsibility of "Turkiye Klinikleri", institutions collaborated with "Turkiye Klinikleri", "Turkiye Klinikleri" employee and directors, "Turkiye Klinikleri" authorized salespeople. Commitment to accuracy and legality of the published information, context, visual and auditory images provided by any third party are under the full responsibility of the third party. "Turkiye Klinikleri" does not promise and guarantee the safety, accuracy and legality of the services and context provided by a third party.

4.4. "USER"s cannot act against "Turkiye Klinikleri", other "USER"s and third parties by using the "SITE". "Turkiye Klinikleri" has no direct and/or indirect responsibility for any damage a third party suffered or will suffer regarding "USER"s actions on the "SITE" against the rules of the hereby "Terms of Use" and the law.

4.5. "USER"s accept and undertake that the information and context they provided to the "SITE" are accurate and legal. "Turkiye Klinikleri" is not liable and responsible for promising and guaranteeing the verification of the information and context transmitted to "Turkiye Klinikleri" by the "USER"s, or uploaded, changed and provided through the "SITE" by them and whether these information are safe, accurate and legal.

4.6. "USER"s agree and undertake that they will not perform any action leading to unfair competition, weakening the personal and commercial credit of "Turkiye Klinikleri" and a third party,  encroaching and attacking on personal rights within the "SITE" in accordance with the Turkish Commercial Code Law.

4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com