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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. Melancholia. 2009. The Wellcome Trust Case Control Consortium Is Behavior Different?. 14,000 Cases 3,000 Controls. WGA’s of Schizophrenia. MCH: major histocompatibility complex HIST1H2BJ: histone

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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 Melancholia

  3. 2009

  4. The Wellcome Trust Case Control ConsortiumIs Behavior Different? 14,000 Cases 3,000 Controls

  5. 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

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

  7. Power in Association Studies

  8. Make the Effect Large

  9. Focus on Anorexia Nervosa • Defined by diet restriction - weight <85% ideal BMI • female risk >>> male risk • Onset during adolescence • High comorbidity with anxiety disorders • Accompanied by obsessive, rigid, perfectionistic personality traits • Strong resistance to re-feeding (food phobia) • SSRI’s not effective in underweight state, can prevent relapse and treat anxiety/personality traits.

  10. Fear learning model of Anorexia Nervosa

  11. Focus on the Serotonin Transporter

  12. AAAAAAA AAAAAAAA Messenger RNA produced from the SERT gene is processed into two forms: rs3813034 ~0.45 in Caucasians

  13. * * Gender difference in vs. Forms of SERT

  14. rs3813034 genotype influences vs. forms of SERT

  15. * * vs. Forms of SERTVary Across Development

  16. * SSRI’s Increases the vs. Form of SERT

  17. 60% by weight 60% by weight 60% Diet Restriction as a Model of Anorexia Nervosa

  18. Diet Restriction induces the vs. Form of SERT

  19. Revisiting the vs. Forms of SERTin the Fear Learning Model of Anorexia Nervosa

  20. Refeeding Female gender Anxiety Harm Avoidance Obsessiveness Perfectionism Diet restriction SSRI Rx Reduced Anxiety Crusty personality Adolescence 60% by weight Risk alleles of rs3813034

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