Davranışsal ve Sosyal Genomikte Nasıl Bir Nedensellik Kavramına İhtiyacımız Var?

Year 2024, Issue: 22, 157 - 170, 12.12.2024

Gökhan Akbay

https://doi.org/10.55256/temasa.1552643

Abstract

Bu makalede, davranış genetiği ve sosyogenomik gibi alanlarda genlerin etkilerini nasıl gösterdiklerini en iyi şekilde ifade eden nedensellik kavramının taşıması gereken özellikler incelenecektir. İlk olarak düzenliliğe dayalı, mekanik ve fark yaratmaya dayalı nedensellik kavramları analiz edilecek ve bunlardan hangisinin bahsi geçen alanlardaki bilim insanları tarafından yaygın olarak kullanıldığı saptanacaktır. Bu çalışmada ortaya çıkan sonuçlara göre genom düzeyinde ilişkilendirme çalışmalarında genetik nedensellikten anlaşılan, fark yaratmaya dayalı, müdahale kuramı ekseninde bir nedensellik kavramıdır. Bu yaklaşımda nedensellik, olguyu bütün veçheleriyle ortaya çıkaran tüm koşul, süreç ve aktivitelerin toplamı değildir. Neden, karşılaştırılan gerçek veya varsayımsal durumların farklarını açıklayan bir faktör veya faktörler kümesidir. Müdahale ise ideal bir deneydir. Başta Judea Pearl ve James Woodward olmak üzere, çeşitli bilim felsefecileri tarafından açımlanan bu kavrayış, ilgili alanlardaki mevcut kullanımı doğru yansıtmakla birlikte, mevzubahis genomik yöntemler deneysel çalışmalarla desteklenmediği sürece, genler ve karmaşık fenotipler arasındaki ilişki korelasyondan öteye geçmeyecek ve müdahale kuramının nedensellik atfı koşullarını karşılayamayacaktır. Mekanik nedensellik kuramı nedensel ilişkileri daha zengin biçimde yansıtması açısından avantajlıdır, ancak daha zayıf kriterlerin bile karşılanamadığı bir durumda mekanistik modellerin geliştirilmesi oldukça zordur.

Keywords

Nedensellik, GWAS, Müdahale Kuramı, Davranış Genetiği, Mekanizmacılık

Supporting Institution

TÜBİTAK

Project Number

1059B192202453 numaralı TÜBİTAK-2219 Yurtdışı Doktora Sonrası Araştırma Bursu

What Kind Of A Causality Concept Do We Need İn Behavioral And Social Genomics?

Abstract

In this paper, we will examine the properties of the concept of causality that best reflects how genes exert their effects in fields such as behavioral genetics and sociogenomics. First, regularity-based, mechanistic and difference-making causality concepts will be analyzed, and we will identify which of these is commonly used by scientists in the aforementioned fields. According to the results of this study, what is understood as genetic causality in genome-wide association studies is a difference-making concept of causality in line with the interventionist theory. In this approach, causality is not the sum total of all the conditions, processes and activities that bring about the phenomenon with all its facets. The cause is a factor or set of factors that explains the differences between the actual or hypothetical situations being compared. An intervention is an ideal experiment. This notion, which has been elucidated by various philosophers of science, especially by Judea Pearl and James Woodward, accurately reflects current usage in the fields mentioned. However, unless these genomic methods are supported by experimental studies, the relationship between genes and complex phenotypes will not go beyond correlation and satisfy the conditions of the interventionist theory. Mechanistic causation theory has the advantage of capturing causal relationships in a richer way, but it is very difficult to develop mechanistic models when even weaker criteria cannot be met.

Keywords

Causality, GWAS, İnterventionist Theory, Behavioral Genetics, Mechanism

Project Number

1059B192202453 numaralı TÜBİTAK-2219 Yurtdışı Doktora Sonrası Araştırma Bursu

References

• Baronas, John M., Eric Bartell, Anders Eliasen, John G. Doench, Loic Yengo, Sailaja Vedantam, Eirini Marouli, Henry M. Kronenberg, Joel N. Hirschhorn ve Nora E. Renthal. “Genome-Wide CRISPR Screening of Chondrocyte Maturation Newly Implicates Genes in Skeletal Growth and Height-Associated GWAS Loci,” Cell Genomics 3, sayı: 5 (May 10, 2023): 100299. https://doi.org/10.1016/j.xgen.2023.100299
• Bechtel, William ve Robert C. Richardson. Discovering Complexity : Decomposition and Localization as Strategies in Scientific Research. [MIT Press ed.]. Cambridge, Massachusetts: The MIT Press, 2010.
• Craver, Carl F. ve Lindley Darden. In Search of Mechanisms : Discoveries across the Life Sciences. Chicago: University of Chicago Press, 2013.
• Dawkins, Richard. The Extended Phenotype : The Gene as the Unit of Selection. Oxford [Oxfordshire]: Freeman, 1982.
• Gould, Stephen Jay. The Mismeasure of Man. The Mismeasure of Man. Rev. and Expanded. New York: W.W. Norton, 1996.
• Harden, Kathryn Paige. The Genetic Lottery : Why DNA Matters for Social Equality. Princeton, New Jersey: Princeton University Press, 2021.
• Judson, Horace Freeland. The Eighth Day of Creation : Makers of the Revolution in Biology. Expanded ed. Plainview, N.Y: CSHL Press, 1996.
• Lewis, David. “Causation,” The Journal of Philosophy 70, sayı: 17 (1973): 556–67. https://doi.org/10.2307/2025310
• ———. “Causation as Influence,” The Journal of Philosophy 97, sayı: 4 (2000): 182–97. https://doi.org/10.2307/2678389
• Lewontin, Richard C., Steven P. R. Rose ve Leon J. Kamin. Not in Our Genes: Biology, Ideology, and Human Nature. 1st ed. New York: Pantheon Books, 1984.
• Liu, Shujing, Shiyu Song, Shuan Wang, Tonghui Cai, Lian Qin, Xinzhuang Wang, Guangming Zhu, et al. “Hypothalamic FTO Promotes High-Fat Diet-Induced Leptin Resistance in Mice through Increasing CX3CL1 Expression,” The Journal of Nutritional Biochemistry 123, (January 2024): 109512. https://doi.org/10.1016/j.jnutbio.2023.109512
• Loos, Ruth J. F. ve Giles S. H. Yeo. “The Genetics of Obesity: From Discovery to Biology,” Nature Reviews Genetics 23, sayı: 2 (February 2022): 120-33. https://doi.org/10.1038/s41576-021-00414-z
• Mackie, J. L. “Causes and Conditions,” American Philosophical Quarterly (Oxford) 2, sayı: 4 (1965): 245-64.
• ———. The Cement of the Universe; a Study of Causation. Oxford: Clarendon Press, 1974.
• Madole, James W. ve K. Paige Harden. “Building Causal Knowledge in Behavior Genetics,” The Behavioral and Brain Sciences 46, (May 2022): e182. https://doi.org/10.1017/S0140525X22000681
• Morgan, Thomas Hunt, Alfred Henry Sturtevant, Hermann Joseph Muller ve Calvin Blackman Bridges. The Mechanism of Mendelian Heredity. Holt, 1922.
• Mostafavi, Hakhamanesh, Arbel Harpak, Ipsita Agarwal, Dalton Conley, Jonathan K Pritchard ve Molly Przeworski. “Variable Prediction Accuracy of Polygenic Scores within an Ancestry Group,” eLife 9, (January 2020): e48376. https://doi.org/10.7554/eLife.48376
• O’Connor, Luke J., Armin P. Schoech, Farhad Hormozdiari, Steven Gazal, Nick Patterson ve Alkes L. Price. “Extreme Polygenicity of Complex Traits Is Explained by Negative Selection,” The American Journal of Human Genetics 105, sayı: 3 (September 2019): 456-76. https://doi.org/10.1016/j.ajhg.2019.07.003
• Okbay, Aysu, Yeda Wu, Nancy Wang, Hariharan Jayashankar, Michael Bennett, Seyed Moeen Nehzati, Julia Sidorenko, et al. “Polygenic Prediction of Educational Attainment within and between Families from Genome-Wide Association Analyses in 3 Million Individuals,” Nature Genetics 54, sayı: 4 (April 2022): 437-49. https://doi.org/10.1038/s41588-022-01016-z
• Pearl, Judea. Causality : Models, Reasoning, and Inference. 2nd edition. Cambridge: Cambridge University Press, 2000.
• ———. “The Structural Theory of Causation” in Causality in the Sciences, Editörler: Jon Williamson, Federica Russo ve Phyllis McKay Illari, 697–727. Oxford: Oxford University Press, 2011.
• Peluffo, Alexandre E. “The ‘Genetic Program’: Behind the Genesis of an Influential Metaphor,” Genetics (Austin) 200, sayı: 3 (2015): 685-96. https://doi.org/10.1534/genetics.115.178418
• Plomin, Robert. Blueprint : How DNA Makes Us Who We Are. Cambridge, UNITED STATES: MIT Press, 2018. http://ebookcentral.proquest.com/lib/utxa/detail.action?docID=5583688
• Proctor, Robert N. “The History of the Discovery of the Cigarette–Lung Cancer Link: Evidentiary Traditions, Corporate Denial, Global Toll,” Tobacco Control 21, sayı: 2 (2012): 87-91. https://doi.org/10.1136/tobaccocontrol-2011-050338
• Psillos, Stathis. “The Idea of Mechanism,” in Causality in the Sciences, Editörler: Jon Williamson, Federica Russo ve Phyllis McKay Illari, 771–88. Oxford: Oxford University Press, 2011.
• Psillos, Stathis ve Stavros Ioannidis. “Mechanistic Causation: Difference-Making Is Enough,” Teorema: Revista Internacional de Filosofía 38, sayı: 3 (2019): 53-76. https://www.jstor.org/stable/26874512
• Ross, Lauren ve James Woodward. “Causal Approaches to Scientific Explanation” in The Stanford Encyclopedia of Philosophy, Editöler: Edward N. Zalta ve Uri Nodelman, Spring 2023. Metaphysics Research Lab, Stanford University, 2023. https://plato.stanford.edu/archives/spr2023/entries/causal-explanation-science/
• Russell, Bertrand. “On the Notion of Cause,” Proceedings of the Aristotelian Society 13, (1912): 1-26. https://www.jstor.org/stable/4543833
• Russo, Federica ve Jon Williamson. “Interpreting Causality in the Health Sciences,” International Studies in the Philosophy of Science 21, sayı: 2 (July 2007): 157-70. https://doi.org/10.1080/02698590701498084
• Schrenk, Markus Andreas. Metaphysics of Science : A Systematic and Historical Introduction. First edition. New York: Routledge, 2016. https://doi.org/10.4324/9781315639116
• Stoltenberg, Scott F. Foundations of Behavior Genetics. Cambridge, United Kingdom: Cambridge University Press, 2023.
• Trubetskoy, Vassily, Antonio F. Pardiñas, Ting Qi, Georgia Panagiotaropoulou, Swapnil Awasthi, Tim B. Bigdeli, Julien Bryois, et al. “Mapping Genomic Loci Implicates Genes and Synaptic Biology in Schizophrenia,” Nature 604, sayı: 7906 (April 2022): 502-8. https://doi.org/10.1038/s41586-022-04434-5
• Waters, C. Kenneth. “Causes That Make a Difference,” The Journal of Philosophy 104, sayı: 11 (2007): 551-79. https://www.jstor.org.ezproxy.lib.utexas.edu/stable/20620058
• Woodward, James. “Causation in Biology: Stability, Specificity, and the Choice of Levels of Explanation,” Biology & Philosophy 25, sayı: 3 (June 2010): 287-318. https://doi.org/10.1007/s10539-010-9200-z
• Woodward, James F. Making Things Happen: A Theory of Causal Explanation. Oxford Studies in Philosophy of Science. New York: Oxford University Press, 2003.
• Woodward, James F. (James Francis). Causation with a Human Face : Normative Theory and Descriptive Psychology. New York, NY: Oxford University Press, 2021.