Shared genetic architecture of brain age gap across 30 cohorts worldwide

Baltramonaityte, V., Jawinski, P., Staginnus, M., Shahisavandi, M., Kovacs, B. Z., Schuurmans, I. K., Constantinides, C., Hariri, A. R., Teumer, A., Rodrigue, A. L., Tsuchida, A., Manzouri, A., Karuk, A., Fuertjes, A. E., Lella, A., Knodt, A. R., Juellig, A., Caspi, A., Crespo-Facorro, B., Penninx, B. W., Lavebratt, C., Lochner, C., Yasuda, C. L., Alnaes, D., Stein, D. J., Mathalon, D. H., Glahn, D. C., Klose, D., Kiltschewskij, D. J., Pomarol-Clotet, E., Bruxel, E. M., Crivello, F., Cendes, F., Davies, G., Salum, G. A., Grabe, H. J., Zar, H. J., Tiemeier, H., Voelzke, H., Lemaitre, H., Lopes-

Department of Psychology, University of Bath, Bath, United Kingdom · medrxiv

Paper

Abstract

Multiple brain age prediction models have been developed using diverse methodological approaches. However, it remains unclear whether these models capture a shared genetic signal. We first conducted a new brain age gap (BAG) GWAS in 60,735 subjects across 29 cohorts worldwide, and then applied genomic structural equation modelling to examine the shared genetic variance with five prior BAG GWASs using a single latent BAG factor (30 cohorts overall). All six BAG GWASs loaded onto a single factor (R2=63%, 19 SNPs). Genetically, the BAG factor was positively correlated with multiple traits, with blood pressure, smoking, longevity, autism, and sleep showing putatively causal effects. Polygenic score (PGS) associations with BAG were observed already in childhood. BAG factor PGS captured more associations with health traits than individual BAG PGSs, suggesting that the shared signal may provide a more sensitive marker of brain health than any single model alone.

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Research summary

The paper claims that a shared genetic architecture underlies brain age gap across multiple cohorts, which may serve as a sensitive marker of brain health. This research is relevant as it explores genetic factors that could influence aging processes and longevity, potentially identifying pathways that contribute to healthier aging.

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