Genetics Group

Niladri Banerjee defends his PhD

The Martens Group is proud to announce Niladri's successful defence of his PhD thesis entitled "An evolutionary epigenetics approach to schizophrenia." Niladri received main supervision by Stéphanie Le Hellard (UiB) and co-supervision by Timothy Hughes, (UiO), and Tatiana Polushina (UiB).

PhD candidate Martens Group
Foto/ill.: Fotograf Kirsten Sjøwall

Main content

Schizophrenia is a psychotic disorder with an estimated lifetime prevalence of ~1% worldwide. Despite reduced fecundity of patients, this rate is stable across population groups separated by geography and time. There is also evidence from the Mesopotamian culture ca 5000 years ago of symptoms that today would be classified as schizophrenia. To explain this stable occurrence of the disorder, the so-called ‘Evolutionary hypothesis of schizophrenia’ has been gaining ground. The most well known of which was propositioned by T.J. Crow in 1998, though others including Huxley (1964) and Essen-Möller (1959) have also argued about selective advantages of the disorder. A key assertion made by Crow was the emergence of schizophrenia as a by-product of human evolution, as ‘the price humans pay for language’.

In the past two decades, the emergence of genomic technologies and resources have made it possible to test the evolutionary aspect of Crow’s hypothesis. There is a growing body of evidence from the field of genomics that suggests human evolution may have played a role in the susceptibility to schizophrenia.

Developments within the last five years have allowed researchers to trace the evolution of epigenomes giving an unprecedented window on gene-environment (GxE) interactions of the past several thousand to millions of years. In the present thesis, I undertake a body of work that investigates the evolutionary question of schizophrenia from this new field of evolutionary epigenetics. We first test whether human-specific methylated regions, determined in comparison to Neanderthals and Denisovans are enriched for schizophrenia markers. These methylated regions represent at least 750,000 years of evolution since the last common ancestor diverged from Neanderthals and Denisovans (Paper I). This was followed up by investigating primate-methylated regions that represent at least 13 MYA of epigenomic evolution (Paper II). Finally, we investigate whether human-specific methylated regions, as defined in the first study are amenable to methylation variation in patients with schizophrenia (Paper III).

We find evidence that recent evolution denoted by human-specific methylated regions tracing ~750,000 years of methylation development are enriched for schizophrenia markers. Primate methylation markers are not enriched for schizophrenia variants with the exception of the extended Major-Histocompatibility Region (MHC) region. Finally, we find evidence of methylation disruption in brain samples of patients with schizophrenia in regions that underwent human-specific methylation evolution.

Our results provide support that recent evolution, denoted by methylation changes since the divergence of the common ancestor of humans, Neanderthals and Denisovans, harbour more schizophrenia associated markers than expected by chance, and thus, may have played a role in susceptibility to schizophrenia at a group-level.

The disputas took place on September 28th, 2018, Professor Kerry Ressler, Harvard Medical School, USA (First opponent), Professor Eivind Hovig, Oslo University Hospital (Second opponent), and Professor Valeriya Lyssenko, Universitetet i Bergen, (committee member). The Disputasen as led by Professor Emeritus Oddmund Søvik (UiB).