Shared genes and pathways in dementia: Insights from genome-wide association studies

Dementia, a collective term for neurodegenerative disorders marked by cognitive decline, affects millions worldwide, and is expected to rise significantly in prevalence. Genome-wide association studies (GWASs), as highlighted in this review, have revolutionized our understanding of dementia by identifying contributing genetic loci and pathways, including for Alzheimer's disease, vascular dementia, frontotemporal lobar dementia, and Lewy body dementia. This review critically analyzes published findings to shed insight on shared genes and pathways, encompassing lipid metabolism, immune responses, lysosomal mechanisms, and ionic homeostasis, which underlie neurodegeneration in dementia. We discuss methodological advances, challenges posed by genetic heterogeneity and population diversity, and the utility of polygenic risk scores in disease prediction. Furthermore, the importance of integrating tissue-specific expression data and non-European ancestral study cohorts is emphasized. Finally, this review outlines the next steps for advancing dementia research through GWASs and genetic insights. HIGHLIGHTS: Genome-wide association studies (GWASs) provide insight into the complex genetic architecture underlying dementia. Synthesizing GWASs across dementia subtypes highlights shared mechanisms. Identifying shared pathways may guide therapeutic development. Limitations exist and future GWASs may benefit from use of diverse populations.