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Depression in diverse populations: Unravelling the interplay between genes and environment

Objective

Depression affects 300 million people and represents one of the biggest challenges to human health to date. Of the burden, 80% pertains to low- and middle-income countries. It is thus imperative to understand the global causes of depression to design effective targeted interventions. DIVERGE will build the first ancestrally diverse data resource for depression, generated from biobanks (N=1.8M) and new studies in Pakistan (N=20K) as well as sub-Saharan Africa (N=13K) with deep phenotyping and genotyping.

Differences in depression risk between populations have been shaped by the environment, demography and diverging evolutionary history. Using the novel perspective of evolutionary psychiatry, DIVERGE will comprehensively characterise the genetic architecture of depression and assess how it has been shaped by natural selection. Thereby, I will illuminate how heritability, environmental factors and their interplay affect disease development. I will develop a new method, trans-ethnic colocalization, to address the fundamental question whether genetic risk factors are transferable across populations. This is important to ensure that health benefits of precision medicine can be shared within and across populations.

In addition to the big picture approach, I aim to identify specific causes of the disorder. The diversity of the data together with the application of population-matched inheritance models will empower the discovery of novel genetic loci for depression. I will develop and apply cutting-edge methods, including trans-ethnic fine-mapping with functional annotations to uncover biological mechanisms underlying depression loci. Trauma, such as exposure to violence, is a strong risk factor for depression. DIVERGE will investigate the interplay between traumatic life events and genetic susceptibility which could help understand how mental illness differs across groups. These innovations will lead to a step change in our understanding of the aetiology of depression.

Call for proposal

ERC-2020-STG
See other projects for this call

Funding Scheme

ERC-STG - Starting Grant

Host institution

UNIVERSITY COLLEGE LONDON
Address
Gower Street
WC1E 6BT London
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 2 033 506,25

Beneficiaries (2)

UNIVERSITY COLLEGE LONDON
United Kingdom
EU contribution
€ 2 033 506,25
Address
Gower Street
WC1E 6BT London
Activity type
Higher or Secondary Education Establishments
LAHORE INSTITUTE OF RESEARCH AND DEDEVELOPMENT TRUST
Pakistan
EU contribution
€ 462 443,75
Address
Rehman Arcade Office 1 2Nd Floor Mian Airline Blvd
54000 Lahore
Activity type
Research Organisations