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Changing perspectives: Towards detailed phenotyping in genetics

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  • Nagel, Mats

Abstract

Mental health problems are highly prevalent in modern-day society. Despite several decades of intensive research aimed at identifying the underlying biological mechanisms, and potential drug targets, pharmacological treatments still have limited success. Since all traits are at least partially influenced by our genetic makeup, using genetic information to increase our understanding of the biological mechanisms underlying mental health problems might eventually benefit patients. Genome-wide association studies (GWAS) provide an exploratory way to identify genetic variants throughout the genome that are, statistically, associated to a trait of interest. The explosion of GWAS studies since 2005 (https://www.ebi.ac.uk/gwas/diagram) has drastically increased our knowledge of the biology of diseases and identified thousands of variants involved in a wide variety of (disease) traits. Yet for many complex traits, like psychiatric disorders, the identified genetic variants explain only a fraction of the variance in the trait. We argue that this may, in part, be the result of the way in which neuropsychiatric traits are operationalized in genetic studies. Typically, participants are classified as cases (i.e., people that suffer from a given psychiatric disorder) or as controls (i.e., not suffering from that particular disorder). However, people suffering from the same disorder may exhibit different sets of symptoms that may, in turn, be influenced by different genetic variants. In other words, the manner in which phenotypes are operationalized will have consequences for the success of genetic analyses. Therefore, in order to properly study the genetic basis of complex behavior, it is vital to think about the exact nature of the phenotypes used in the analysis, and the way they are operationalized. This thesis uses large-scale genetic data and state-of-the-art methods to study the merits of more detailed phenotyping in uncovering the genetics of complex neuropsychiatric traits.

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  • Nagel, Mats, 2020. "Changing perspectives: Towards detailed phenotyping in genetics," Thesis Commons a4nz2, Center for Open Science.
    • Handle: RePEc:osf:thesis:a4nz2
    DOI: 10.31219/osf.io/a4nz2
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    1. Irving Kirsch & Brett J Deacon & Tania B Huedo-Medina & Alan Scoboria & Thomas J Moore & Blair T Johnson, 2008. "Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration," PLOS Medicine, Public Library of Science, vol. 5(2), pages 1-9, February.
    2. Magnus Johannesson & David I. Laibson & Sarah E. Medland & Michelle N. Meyer & Joseph K. Pickrell & Tõnu Esko & Robert F. Krueger & Jonathan P. Beauchamp & Philipp D. Koellinger & Daniel J. Benjamin &, 2016. "Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses," Post-Print hal-02017373, HAL.
    3. Gad Abraham & Michael Inouye, 2014. "Fast Principal Component Analysis of Large-Scale Genome-Wide Data," PLOS ONE, Public Library of Science, vol. 9(4), pages 1-5, April.
    4. Chuong B Do & Joyce Y Tung & Elizabeth Dorfman & Amy K Kiefer & Emily M Drabant & Uta Francke & Joanna L Mountain & Samuel M Goldman & Caroline M Tanner & J William Langston & Anne Wojcicki & Nicholas, 2011. "Web-Based Genome-Wide Association Study Identifies Two Novel Loci and a Substantial Genetic Component for Parkinson's Disease," PLOS Genetics, Public Library of Science, vol. 7(6), pages 1-14, June.
    5. Lee, James J. & McGue, Matt & Iacono, William G. & Michael, Andrew M. & Chabris, Christopher F., 2019. "The causal influence of brain size on human intelligence: Evidence from within-family phenotypic associations and GWAS modeling," Intelligence, Elsevier, vol. 75(C), pages 48-58.
    6. Chao Tian & Robert M Plenge & Michael Ransom & Annette Lee & Pablo Villoslada & Carlo Selmi & Lars Klareskog & Ann E Pulver & Lihong Qi & Peter K Gregersen & Michael F Seldin, 2008. "Analysis and Application of European Genetic Substructure Using 300 K SNP Information," PLOS Genetics, Public Library of Science, vol. 4(1), pages 1-11, January.
    7. Christiaan A de Leeuw & Joris M Mooij & Tom Heskes & Danielle Posthuma, 2015. "MAGMA: Generalized Gene-Set Analysis of GWAS Data," PLOS Computational Biology, Public Library of Science, vol. 11(4), pages 1-19, April.
    8. Eric S. Lander, 2011. "Initial impact of the sequencing of the human genome," Nature, Nature, vol. 470(7333), pages 187-197, February.
    9. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    10. Aysu Okbay & Jonathan P. Beauchamp & Mark Alan Fontana & James J. Lee & Tune H. Pers & Cornelius A. Rietveld & Patrick Turley & Guo-Bo Chen & Valur Emilsson & S. Fleur W. Meddens & Sven Oskarsson & Jo, 2016. "Genome-wide association study identifies 74 loci associated with educational attainment," Nature, Nature, vol. 533(7604), pages 539-542, May.
    11. Christiaan A. Leeuw & Sven Stringer & Ilona A. Dekkers & Tom Heskes & Danielle Posthuma, 2018. "Conditional and interaction gene-set analysis reveals novel functional pathways for blood pressure," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    12. Mats Nagel & Kyoko Watanabe & Sven Stringer & Danielle Posthuma & Sophie Sluis, 2018. "Item-level analyses reveal genetic heterogeneity in neuroticism," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    13. Chabris, C. F. & Lee, J. J. & Cesarini, D. & Benjamin, D. J. & Laibson, David I., 2015. "The Fourth Law of Behavior Genetics," Scholarly Articles 30780203, Harvard University Department of Economics.
    14. Robert Plomin, 1999. "Genetics and general cognitive ability," Nature, Nature, vol. 402(6761), pages 25-29, December.
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