Professor Smith's research interests are in four main areas:

• The genetic epidemiology of mood disorders (particularly bipolar disorder)
• Data science and mental health informatics research
• Understanding comorbidity between mental and physical health disorders
• Sleep and circadian health as they relate to mood disorders

His group has been at the forefront of mental health research using data from the UK Biobank cohort and he is part of several global research collaborations, including the Psychiatric Genomics Consortium, the Consortium for Lithium Genomics and the Chronobiology Task Force of the International Society for Bipolar Disorder.