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Bottom(s) Up! A biological approach to behavioral genetics

Bottom(s) Up! A biological approach to behavioral genetics. Two Approaches to Human Genetics. Phenotypic Effects of Individual Polymorphisms are small. WGA’s of Schizophrenia. MCH: major histocompatibility complex HIST1H2BJ: histone PRSS16: serineprotease 16

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Bottom(s) Up! A biological approach to behavioral genetics

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  1. Bottom(s) Up!A biological approach to behavioral genetics

  2. Two Approaches to Human Genetics

  3. Phenotypic Effects of Individual Polymorphisms are small

  4. WGA’s of Schizophrenia MCH: major histocompatibility complex HIST1H2BJ: histone PRSS16: serineprotease 16 PGBD1: piggyBac transposable element derived 1 NOTCH4: notch4 NRGN: neurogranin TCF4: transcription factor 4

  5. Many SNP’s of Small Effect Size Contribute to Risk for SCZ n = 8,537 16,124 23,563 31,029 37,655

  6. Power in Association Studies

  7. Make the Effect Large

  8. Structural Neuroimaging - The New Phrenology?

  9. Radioligand Imaging Identifies Neurochemical Effects

  10. fMRI Identifies Neurobehavioral Effects

  11. Functional Connectivity Analysis Identifies Affected Circuits

  12. L Homozygotes < S Carriers L Homozygotes > S Carriers Multiple Testing on the Phenotype Side

  13. Meta-Analysis of 5HTTLPR and Amygdala Activation

  14. Vertical Approach Refines Hypotheses

  15. Focus on the Serotonin Transporter

  16. rs3813034 Polyadenylation Polymorphism in SERT

  17. Yes, rs3813034 Has a Molecular Phenotype

  18. What Else Do We Know About the SERT DPF?

  19. Anything Else?

  20. That Sounds Like the Circuitry of theEmotional Go/NoGo Task

  21. And Males Habituate Better Than Females in the Emotional Go/NoGo

  22. Can We Use All This Information to Develop a Model of rs3813034 Effects on Performance in the Emo Go/NoGo?

  23. Does the Model Work?

  24. Association of rs3813034 and Panic Disorder What About Disease?

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