Public Defence: Saurabh Srinivasan

MSc Saurabh Srinivasan at Institute of Clinical Medicine will be defending the thesis “A Polygenic Enrichment Approach to Human Evolution in Schizophrenia and Cognitive Function” for the degree of PhD (Philosophiae Doctor).

Trial Lecture – time and place

See Trial Lecture.

Adjudication committee

  • First opponent: Professor Leif Edward Ottesen Kennair, Department of Psychology, Norwegian University of Science and Technology (NTNU)
  • Second opponent: Senior Researcher Bjørn Grinde, Division of Mental and Physical Health, Norwegian Institute of Public Health
  • Third member and chair of the evaluation committee: Associate Professor Elfrida H. Kvarstein, Faculty of Medicine, University of Oslo

Chair of the Defence

Professor Emeritus Berit Grøholt, Faculty of Medicine, University of Oslo

Principal Supervisor

Professor Ole A. Andreassen, Faculty of Medicine, University of Oslo

Summary

The genomic regions involved in evolution of modern humans are more likely to be associated with schizophrenia and cognitive function.

Srinivasan has shown that the regions undergoing positive selection in humans after divergence from Neanderthals are enriched of genetic variants associated with schizophrenia and cognitive function. The enrichment observed in schizophrenia is distinct from that observable in other human traits and disorders and remains significant after controlling for confounding factors. The candidate could not find conclusive evidence of any special involvement of older evolutionary markers such as ohnologs, segmental duplications or human accelerated regions. Their enrichment does not remain significant after controlling for introns, exons and untranslated regions (UTR) affiliations.

The aims of the thesis were to increase our understanding of the evolution and development of complex human phenotypes. Primarily, focussing on schizophrenia and neurocognitive function after the human-Neanderthal split, and secondarily investigating older evolutionary markers. The Neanderthal selective sweep score was used to determine if genetic variants associated with evolutionarily relevant, psychiatric disorders and cognitive traits are associated with regions of recent human origin (post human-Neanderthal split). Other evolutionary markers such as segmental duplications, ohnologs and human accelerated regions, which represent earlier stages of primate and ape evolution, were also used to determine whether these regions too are associated with schizophrenia.

Researchers have been fascinated by the evolutionary enigma of schizophrenia, as it seems immune to selective forces even if it reduces fecundity. The current findings place these complex human disorders and traits in an evolutionary context and support theories suggesting that the cognitive complexity that defined modern humans is also associated with increased vulnerability to schizophrenia.

Additional information

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Published May 28, 2019 1:58 PM - Last modified May 28, 2019 3:17 PM