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000282329 0247_ $$2doi$$a10.1101/2025.11.14.25340228
000282329 037__ $$aDZNE-2025-01290
000282329 1001_ $$0P:(DE-2719)9002176$$aMantey, Richard$$b0$$eFirst author
000282329 245__ $$aTandem Repeat Polymorphisms Are Associated with Brain Structure: Results of Two Large Population-based Studies
000282329 260__ $$c2025
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000282329 520__ $$aAlthough genome-wide association studies (GWAS) have uncovered many genetic variants linked to brain structure, much of its heritability remains unexplained. Short tandem repeats (STRs), which are rarely considered in GWAS, may contribute to this “missing heritability”. Using targeted deep sequencing, we systematically assessed the relationship between ∼3000 polymorphic STRs and brain imaging-derived phenotypes across 2958 participants of the Rhineland Study. Expansion of an intronic CA repeat in PRR14L was associated with larger thalamic volume (standardized β [95% CI]=0.15 [0.06–0.24]), while AATG repeat polymorphisms in NADK were associated with reduced subcortical gray matter volume (–0.05 [–0.08 to –0.01]). Both associations replicated in the UK Biobank cohort (N=38879). Beyond single loci, higher polygenic burden of moderate STR expansions was associated with increased total brain, gray matter, supratentorial, and thalamic volumes. Our findings indicate that moderate STR expansions are region-specific determinants of brain morphology and suggest that STR variability may have evolved to enhance neuroanatomical plasticity and cognitive function.
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000282329 536__ $$0G:(EU-Grant)101041677$$aTRANSIT-ND - Tandem Repeats Associated with Neurogenomic Somatic Instability and Neurodegeneration (101041677)$$c101041677$$fERC-2021-STG$$x1
000282329 536__ $$0G:(DE-HGF)POF4-351$$a351 - Brain Function (POF4-351)$$cPOF4-351$$fPOF IV$$x2
000282329 588__ $$aDataset connected to DataCite
000282329 693__ $$0EXP:(DE-2719)PRECISE-20190321$$5EXP:(DE-2719)PRECISE-20190321$$ePlatform for Single Cell Genomics and Epigenomics at DZNE  University of Bonn$$x0
000282329 7001_ $$0P:(DE-2719)9002875$$aHu, Jialu$$b1
000282329 7001_ $$0P:(DE-2719)9002791$$aTouhidinia, Maryam$$b2
000282329 7001_ $$0P:(DE-2719)9003488$$aButt, Tanzeem$$b3
000282329 7001_ $$0P:(DE-2719)9003532$$aSidky, Ahmed Mokhtar$$b4
000282329 7001_ $$0P:(DE-2719)9002351$$aSobhani, Roohollah$$b5
000282329 7001_ $$0P:(DE-2719)2812449$$aEstrada, Santiago$$b6
000282329 7001_ $$0P:(DE-2719)2812735$$aHaendler, Kristian$$b7
000282329 7001_ $$0P:(DE-2719)9000846$$aDe Domenico, Elena$$b8
000282329 7001_ $$0P:(DE-2719)2812219$$aBeyer, Marc D.$$b9
000282329 7001_ $$0P:(DE-2719)2810403$$aBreteler, Monique M. B.$$b10
000282329 7001_ $$0P:(DE-2719)2812578$$aAziz, N. Ahmad$$b11$$eLast author
000282329 773__ $$a10.1101/2025.11.14.25340228
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000282329 9131_ $$0G:(DE-HGF)POF4-351$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vBrain Function$$x1
000282329 9141_ $$y2025
000282329 9201_ $$0I:(DE-2719)5000071$$kAG Aziz$$lPopulation & Clinical Neuroepidemiology$$x0
000282329 9201_ $$0I:(DE-2719)1012001$$kAG Breteler$$lPopulation Health Sciences$$x1
000282329 9201_ $$0I:(DE-2719)1013035$$kAG Beyer$$lImmunogenomics and Neurodegeneration$$x2
000282329 9201_ $$0I:(DE-2719)1040310$$kAG Reuter$$lArtificial Intelligence in Medicine$$x3
000282329 9201_ $$0I:(DE-2719)1013038$$kAG Schultze$$lClinical Single Cell Omics (CSCO) / Systems Medicine$$x4
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