Symptom Science: Omics Supports Common Biological Underpinnings Across Symptoms

Abstract

For precision health care to be successful, an in-depth understanding of the biological mechanisms for symptom development and severity is essential. Omics-based research approaches facilitate identification of the biological underpinnings of symptoms. We reviewed literature for omics-based approaches and exemplar symptoms (sleep disruption, cognitive impairment, fatigue, gastrointestinal [GI] distress, and pain) to identify genes associated with the symptom or symptoms across disease processes. The review yielded 27 genes associated with more than one symptom. ABCB1 (MDR1), APOE, BDNF, CNR1, COMT, DAT1 (SLC6A3), DRD4, ESR1, HLA-DRB1, IL10, IL1B, IL6, LTA, PTGS2 (COX-2), SLC6A4, and TNF were associated with cognitive impairment and pain, which had the most genes in common. COMT and TNF were related to all symptoms except sleep disruption. IL1B was associated with all symptoms except cognitive impairment. IL10, IL1A, IL1B, IL1RN, IL6, and IL8 (CXCL8) were linked with all the exemplar symptoms in various combinations. ABCB1 (MDR1) and SLC6A4 were associated with cognitive impairment, GI distress, and pain. IL10 and IL6 were linked to cognitive impairment, fatigue, and pain. APOE and BDNF were associated with sleep disruption, cognitive impairment, and pain. The 27 genes were associated with canonical pathways including immune, inflammatory, and cell signaling. The pathway analysis generated a 15-gene model from the 27 as well as 3 networks, which incorporated new candidate genes. The findings support the hypothesis of overlapping biological underpinnings across the exemplar symptoms. Candidate genes may be targeted in future omics research to identify mechanisms of co-occurring symptoms for potential precision treatments.