Approved Research

Identification of genetic variants associated with resilience to schizophrenia, bipolar disorder, major depressive disorder, Alzheimer's disease, and suicide

Lay summary

Mental and behavioral disorders are major contributors to disability according to the World Health Organization. It is thought that risk for common neuropsychiatric and related conditions are mediated by a complex interplay between genetic, environmental, psychological, and social factors. Over the last decade, scientists have accelerated their efforts to understand the basis of common neuropsychiatric disorders, but have done so by focusing virtually all of their attention on identifying risk-increasing genes. While those efforts have led to unprecedented knowledge about the risk for common neuropsychiatric disorders, one critical question remains: are there genetic factors in play that shield people from disease? To answer this question, we propose an innovative study to identify genes that promote resilience. In this context, we conceptualize resilience as resistance to disease and health-related behaviors. The major depression (MDD), schizophrenia (SZ), bipolar disorder (BD), Alzheimer's disease (AD), and suicidal behaviors (SB) in the UK Biobank cohort. 

We devised, pilot-tested, and verified our approach to identify "resilience genes" for SZ in a previous study. We found a genetic signature, which we termed "polygenic resilience score", that shows a protective effect against SZ among genetically high-risk unaffected individuals. Now, with access genomic data and diagnoses in the UK Biobank, we will expand our approach to identify genes associated with resistance to common neuropsychiatric disorders and related conditions among high-risk individuals. Our discoveries will potentially elucidate roles for genes in mental health and behavioral disorders, and, in turn, open avenues to identify novel treatment targets to curtail disease.