IDEAS home Printed from https://ideas.repec.org/a/gam/jmathe/v9y2021i23p3083-d691634.html
   My bibliography  Save this article

In Search of Complex Disease Risk through Genome Wide Association Studies

Author

Listed:
  • Lorena Alonso

    (Life Sciences Department, Barcelona Supercomputing Center (BSC), 08034 Barcelona, Spain)

  • Ignasi Morán

    (Life Sciences Department, Barcelona Supercomputing Center (BSC), 08034 Barcelona, Spain)

  • Cecilia Salvoro

    (Life Sciences Department, Barcelona Supercomputing Center (BSC), 08034 Barcelona, Spain)

  • David Torrents

    (Life Sciences Department, Barcelona Supercomputing Center (BSC), 08034 Barcelona, Spain
    Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain)

Abstract

The identification and characterisation of genomic changes (variants) that can lead to human diseases is one of the central aims of biomedical research. The generation of catalogues of genetic variants that have an impact on specific diseases is the basis of Personalised Medicine, where diagnoses and treatment protocols are selected according to each patient’s profile. In this context, the study of complex diseases, such as Type 2 diabetes or cardiovascular alterations, is fundamental. However, these diseases result from the combination of multiple genetic and environmental factors, which makes the discovery of causal variants particularly challenging at a statistical and computational level. Genome-Wide Association Studies (GWAS), which are based on the statistical analysis of genetic variant frequencies across non-diseased and diseased individuals, have been successful in finding genetic variants that are associated to specific diseases or phenotypic traits. But GWAS methodology is limited when considering important genetic aspects of the disease and has not yet resulted in meaningful translation to clinical practice. This review presents an outlook on the study of the link between genetics and complex phenotypes. We first present an overview of the past and current statistical methods used in the field. Next, we discuss current practices and their main limitations. Finally, we describe the open challenges that remain and that might benefit greatly from further mathematical developments.

Suggested Citation

  • Lorena Alonso & Ignasi Morán & Cecilia Salvoro & David Torrents, 2021. "In Search of Complex Disease Risk through Genome Wide Association Studies," Mathematics, MDPI, vol. 9(23), pages 1-26, November.
  • Handle: RePEc:gam:jmathe:v:9:y:2021:i:23:p:3083-:d:691634
    as

    Download full text from publisher

    File URL: https://www.mdpi.com/2227-7390/9/23/3083/pdf
    Download Restriction: no

    File URL: https://www.mdpi.com/2227-7390/9/23/3083/
    Download Restriction: no
    ---><---

    References listed on IDEAS

    as
    1. Michael C Turchin & Matthew Stephens, 2019. "Bayesian multivariate reanalysis of large genetic studies identifies many new associations," PLOS Genetics, Public Library of Science, vol. 15(10), pages 1-18, October.
    2. Clare Bycroft & Colin Freeman & Desislava Petkova & Gavin Band & Lloyd T. Elliott & Kevin Sharp & Allan Motyer & Damjan Vukcevic & Olivier Delaneau & Jared O’Connell & Adrian Cortes & Samantha Welsh &, 2018. "The UK Biobank resource with deep phenotyping and genomic data," Nature, Nature, vol. 562(7726), pages 203-209, October.
    3. Saikat Banerjee & Lingyao Zeng & Heribert Schunkert & Johannes Söding, 2018. "Bayesian multiple logistic regression for case-control GWAS," PLOS Genetics, Public Library of Science, vol. 14(12), pages 1-27, December.
    4. Luke R. Lloyd-Jones & Jian Zeng & Julia Sidorenko & Loïc Yengo & Gerhard Moser & Kathryn E. Kemper & Huanwei Wang & Zhili Zheng & Reedik Magi & Tõnu Esko & Andres Metspalu & Naomi R. Wray & Michael E., 2019. "Improved polygenic prediction by Bayesian multiple regression on summary statistics," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    5. Florence Lichou & Gosia Trynka, 2020. "Functional studies of GWAS variants are gaining momentum," Nature Communications, Nature, vol. 11(1), pages 1-4, December.
    6. Teri A. Manolio & Francis S. Collins & Nancy J. Cox & David B. Goldstein & Lucia A. Hindorff & David J. Hunter & Mark I. McCarthy & Erin M. Ramos & Lon R. Cardon & Aravinda Chakravarti & Judy H. Cho &, 2009. "Finding the missing heritability of complex diseases," Nature, Nature, vol. 461(7265), pages 747-753, October.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Zhen Qiao & Julia Sidorenko & Joana A. Revez & Angli Xue & Xueling Lu & Katri Pärna & Harold Snieder & Peter M. Visscher & Naomi R. Wray & Loic Yengo, 2023. "Estimation and implications of the genetic architecture of fasting and non-fasting blood glucose," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    2. Wenhan Chen & Yang Wu & Zhili Zheng & Ting Qi & Peter M. Visscher & Zhihong Zhu & Jian Yang, 2021. "Improved analyses of GWAS summary statistics by reducing data heterogeneity and errors," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    3. Rikifumi Ohta & Yosuke Tanigawa & Yuta Suzuki & Manolis Kellis & Shinichi Morishita, 2024. "A polygenic score method boosted by non-additive models," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. Parsa Akbari & Olukayode A. Sosina & Jonas Bovijn & Karl Landheer & Jonas B. Nielsen & Minhee Kim & Senem Aykul & Tanima De & Mary E. Haas & George Hindy & Nan Lin & Ian R. Dinsmore & Jonathan Z. Luo , 2022. "Multiancestry exome sequencing reveals INHBE mutations associated with favorable fat distribution and protection from diabetes," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Carla Márquez-Luna & Steven Gazal & Po-Ru Loh & Samuel S. Kim & Nicholas Furlotte & Adam Auton & Alkes L. Price, 2021. "Incorporating functional priors improves polygenic prediction accuracy in UK Biobank and 23andMe data sets," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    6. Yosuke Tanigawa & Junyang Qian & Guhan Venkataraman & Johanne Marie Justesen & Ruilin Li & Robert Tibshirani & Trevor Hastie & Manuel A Rivas, 2022. "Significant sparse polygenic risk scores across 813 traits in UK Biobank," PLOS Genetics, Public Library of Science, vol. 18(3), pages 1-21, March.
    7. Margaret Sunitha Selvaraj & Xihao Li & Zilin Li & Akhil Pampana & David Y. Zhang & Joseph Park & Stella Aslibekyan & Joshua C. Bis & Jennifer A. Brody & Brian E. Cade & Lee-Ming Chuang & Ren-Hua Chung, 2022. "Whole genome sequence analysis of blood lipid levels in >66,000 individuals," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    8. Junyang Qian & Yosuke Tanigawa & Wenfei Du & Matthew Aguirre & Chris Chang & Robert Tibshirani & Manuel A Rivas & Trevor Hastie, 2020. "A fast and scalable framework for large-scale and ultrahigh-dimensional sparse regression with application to the UK Biobank," PLOS Genetics, Public Library of Science, vol. 16(10), pages 1-30, October.
    9. Wei Jiang & Ling Chen & Matthew J. Girgenti & Hongyu Zhao, 2024. "Tuning parameters for polygenic risk score methods using GWAS summary statistics from training data," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    10. Matteo Di Scipio & Mohammad Khan & Shihong Mao & Michael Chong & Conor Judge & Nazia Pathan & Nicolas Perrot & Walter Nelson & Ricky Lali & Shuang Di & Robert Morton & Jeremy Petch & Guillaume Paré, 2023. "A versatile, fast and unbiased method for estimation of gene-by-environment interaction effects on biobank-scale datasets," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    11. Jacob Joseph & Chang Liu & Qin Hui & Krishna Aragam & Zeyuan Wang & Brian Charest & Jennifer E. Huffman & Jacob M. Keaton & Todd L. Edwards & Serkalem Demissie & Luc Djousse & Juan P. Casas & J. Micha, 2022. "Genetic architecture of heart failure with preserved versus reduced ejection fraction," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    12. Vincent Michaud & Eulalie Lasseaux & David J. Green & Dave T. Gerrard & Claudio Plaisant & Tomas Fitzgerald & Ewan Birney & Benoît Arveiler & Graeme C. Black & Panagiotis I. Sergouniotis, 2022. "The contribution of common regulatory and protein-coding TYR variants to the genetic architecture of albinism," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    13. Natalie DeForest & Yuqi Wang & Zhiyi Zhu & Jacqueline S. Dron & Ryan Koesterer & Pradeep Natarajan & Jason Flannick & Tiffany Amariuta & Gina M. Peloso & Amit R. Majithia, 2024. "Genome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    14. Dick Schijven & Sourena Soheili-Nezhad & Simon E. Fisher & Clyde Francks, 2024. "Exome-wide analysis implicates rare protein-altering variants in human handedness," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    15. Lili Liu & Atlas Khan & Elena Sanchez-Rodriguez & Francesca Zanoni & Yifu Li & Nicholas Steers & Olivia Balderes & Junying Zhang & Priya Krithivasan & Robert A. LeDesma & Clara Fischman & Scott J. Heb, 2022. "Genetic regulation of serum IgA levels and susceptibility to common immune, infectious, kidney, and cardio-metabolic traits," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    16. Sylvia Hartmann & Summaira Yasmeen & Benjamin M. Jacobs & Spiros Denaxas & Munir Pirmohamed & Eric R. Gamazon & Mark J. Caulfield & Harry Hemingway & Maik Pietzner & Claudia Langenberg, 2023. "ADRA2A and IRX1 are putative risk genes for Raynaud’s phenomenon," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    17. Mitchell, Brittany L. & Hansell, Narelle K. & McAloney, Kerrie & Martin, Nicholas G. & Wright, Margaret J. & Renteria, Miguel E. & Grasby, Katrina L., 2022. "Polygenic influences associated with adolescent cognitive skills," Intelligence, Elsevier, vol. 94(C).
    18. Brittany L. Mitchell & Jake R. Saklatvala & Nick Dand & Fiona A. Hagenbeek & Xin Li & Josine L. Min & Laurent Thomas & Meike Bartels & Jouke Hottenga & Michelle K. Lupton & Dorret I. Boomsma & Xianjun, 2022. "Genome-wide association meta-analysis identifies 29 new acne susceptibility loci," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    19. Ilias Georgakopoulos-Soares & Chengyu Deng & Vikram Agarwal & Candace S. Y. Chan & Jingjing Zhao & Fumitaka Inoue & Nadav Ahituv, 2023. "Transcription factor binding site orientation and order are major drivers of gene regulatory activity," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    20. Zichen Zhang & Ye Eun Bae & Jonathan R. Bradley & Lang Wu & Chong Wu, 2022. "SUMMIT: An integrative approach for better transcriptomic data imputation improves causal gene identification," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:gam:jmathe:v:9:y:2021:i:23:p:3083-:d:691634. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: MDPI Indexing Manager (email available below). General contact details of provider: https://www.mdpi.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.