Lifetime brain atrophy estimated from a single MRI: measurement characteristics and genome-wide correlates.

Autor: Fürtjes AE; School of Philosophy, Psychology & Language Sciences, The University of Edinburgh, Edinburgh, United Kingdom.; Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom., Foote IF; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, USA., Xia C; School of Philosophy, Psychology & Language Sciences, The University of Edinburgh, Edinburgh, United Kingdom.; Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom., Davies G; School of Philosophy, Psychology & Language Sciences, The University of Edinburgh, Edinburgh, United Kingdom.; Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom., Moodie J; School of Philosophy, Psychology & Language Sciences, The University of Edinburgh, Edinburgh, United Kingdom.; Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom., Taylor A; School of Philosophy, Psychology & Language Sciences, The University of Edinburgh, Edinburgh, United Kingdom.; Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom., Liewald DC; School of Philosophy, Psychology & Language Sciences, The University of Edinburgh, Edinburgh, United Kingdom.; Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom., Redmond P; School of Philosophy, Psychology & Language Sciences, The University of Edinburgh, Edinburgh, United Kingdom.; Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom., Corley J; School of Philosophy, Psychology & Language Sciences, The University of Edinburgh, Edinburgh, United Kingdom.; Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom., McIntosh AM; Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, United Kingdom., Whalley HC; Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, United Kingdom., Maniega SM; Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, United Kingdom., Hernández MV; Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, United Kingdom., Backhouse E; Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, United Kingdom.; UK Dementia Research Institute, The University of Edinburgh, Edinburgh, UK., Ferguson K; Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, United Kingdom.; UK Dementia Research Institute, The University of Edinburgh, Edinburgh, UK., Bastin ME; Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, United Kingdom., Wardlaw J; Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, United Kingdom., de la Fuente J; Department of Psychology, The University of Texas at Austin, Austin, TX, USA., Grotzinger AD; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, USA., Luciano M; School of Philosophy, Psychology & Language Sciences, The University of Edinburgh, Edinburgh, United Kingdom.; Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom., Hill WD; School of Philosophy, Psychology & Language Sciences, The University of Edinburgh, Edinburgh, United Kingdom.; Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom., Deary IJ; School of Philosophy, Psychology & Language Sciences, The University of Edinburgh, Edinburgh, United Kingdom.; Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom., Tucker-Drob EM; Department of Psychology, The University of Texas at Austin, Austin, TX, USA., Cox SR; School of Philosophy, Psychology & Language Sciences, The University of Edinburgh, Edinburgh, United Kingdom.; Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Nov 07. Date of Electronic Publication: 2024 Nov 07.
DOI: 10.1101/2024.11.06.622274
Abstrakt: A measure of lifetime brain atrophy (LBA) obtained from a single magnetic resonance imaging (MRI) scan could be an attractive candidate to boost statistical power in uncovering novel genetic signals and mechanisms of neurodegeneration. We analysed data from five young and old adult cohorts (MRi-Share, Human Connectome Project, UK Biobank, Generation Scotland Subsample, and Lothian Birth Cohort 1936 [LBC1936]) to test the validity and utility of LBA inferred from cross-sectional MRI data, i.e., a single MRI scan per participant. LBA was simply calculated based on the relationship between total brain volume (TBV) and intracranial volume (ICV), using three computationally distinct approaches: the difference ( ICV-TBV ), ratio ( TBV / ICV ), and regression-residual method (TBV~ICV). LBA derived with all three methods were substantially correlated with well-validated neuroradiological atrophy rating scales ( r = 0.37-0.44). Compared with the difference or ratio method, LBA computed with the residual method most strongly captured phenotypic variance associated with cognitive decline ( r = 0.36), frailty ( r = 0.24), age-moderated brain shrinkage ( r = 0.45), and longitudinally-measured atrophic changes ( r = 0.36). LBA computed using a difference score was strongly correlated with baseline (i.e., ICV; r = 0.81) and yielded GWAS signal similar to ICV ( rg = 0.75). We performed the largest genetic study of LBA to date ( N = 43,110), which was highly heritable ( h 2 SNP GCTA = 41% [95% CI = 38-43%]) and had strong polygenic signal (LDSC h 2 = 26%; mean χ2 = 1.23). The strongest association in our genome-wide association study (GWAS) implicated WNT16 , a gene previously linked with neurodegenerative diseases such as Alzheimer, and Parkinson disease, and amyotrophic lateral sclerosis. This study is the first side-by-side evaluation of different computational approaches to estimate lifetime brain changes and their measurement characteristics. Careful assessment of methods for LBA computation had important implications for the interpretation of existing phenotypic and genetic results, and showed that relying on the residual method to estimate LBA from a single MRI scan captured brain shrinkage rather than current brain size. This makes this computationally-simple definition of LBA a strong candidate for more powerful analyses, promising accelerated genetic discoveries by maximising the use of available cross-sectional data.
Databáze: MEDLINE
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