Higher CALLY index is causally linked to lower dementia risk
Mendelian randomization across more than 265,000 UK Biobank and FinnGen participants linked a higher CALLY score to reduced dementia risk but increased sleep disorder risk.
Molecular Genetics and Genomics
In human participants from the UK Biobank and FinnGen cohorts, researchers evaluated how a composite measure of inflammation, nutrition, and immune status relates to disease risk. The team examined the C-reactive protein-albumin-lymphocyte, or CALLY, index using genetic association tools. A genome-wide association study in 265,409 UK Biobank participants identified 154 genomic loci tied to the index. Next, a phenome-wide association study of 113,747 participants screened 713 phenotypes, revealing 24 significant associations. Two-sample Mendelian randomization confirmed causal protective effects of a higher genetically predicted CALLY index against Alzheimer's disease, Alzheimer's dementia, unspecified dementia, and lipid metabolism disorders. The analysis also showed a causal association between a higher index and an increased risk of sleep disorders. Pleiotropy analyses highlighted shared biological pathways in lipid metabolism and inflammation.
Why it matters
The CALLY index reflects the interplay of chronic inflammation, nutritional state, and immune function, which are central pillars of aging biology. Establishing causal links between this integrated biomarker and dementia highlights how systemic immune-metabolic health shapes late-life neurodegenerative risk.
Caveats
The findings are based on genetic cohorts from the UK Biobank and FinnGen, which may restrict generalizability to other populations. In addition, the observed causal relationship linking a higher index to an increased risk of sleep disorders requires further investigation.
The paper
CRP-albumin-lymphocyte index and multisystem diseases: a phenome-wide Mendelian randomization study
Soochow University
Molecular Genetics and Genomics · 28 Sep 2026