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000282330 005__ 20251121165933.0
000282330 0247_ $$2doi$$a10.1101/2025.11.13.25340159
000282330 037__ $$aDZNE-2025-01291
000282330 1001_ $$0P:(DE-2719)9002875$$aHu, Jialu$$b0$$eFirst author
000282330 245__ $$aGenome-wide profiling of short tandem repeat somatic instability reveals associations with age, sex and brain-related traits
000282330 260__ $$c2025
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000282330 520__ $$aShort tandem repeats (STRs) are highly abundant in the human genome and their age-related somatic instability is emerging as a pivotal pathomechanism in repeat expansion disorders. Nevertheless, currently no analysis tool exists for genome-wide profiling of STR somatic instability. Here, we present searchSTR, a novel computational framework that enables accurate STR genotyping and somatic instability quantification from both whole-genome and targeted sequencing data. Applying this approach, we analyzed STR variants from whole-genome sequencing data of the 1000 Genomes Project (n=3,202) and targeted deep-sequencing data of the population-based Rhineland Study (n=2,974). We provide a comprehensive multiancestry genome-wide reference panel of STR variants and their somatic instability, covering more than 1.4 million STRs across 26 populations. Remarkably, STR somatic instability at many loci was robustly associated with age, sex, brain morphology and markers of neurodegeneration. These findings reveal a crucial role for STR somatic instability as an age-dependent modifier of brain structure.
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000282330 536__ $$0G:(EU-Grant)101041677$$aTRANSIT-ND - Tandem Repeats Associated with Neurogenomic Somatic Instability and Neurodegeneration (101041677)$$c101041677$$fERC-2021-STG$$x1
000282330 536__ $$0G:(DE-HGF)POF4-351$$a351 - Brain Function (POF4-351)$$cPOF4-351$$fPOF IV$$x2
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000282330 693__ $$0EXP:(DE-2719)PRECISE-20190321$$5EXP:(DE-2719)PRECISE-20190321$$ePlatform for Single Cell Genomics and Epigenomics at DZNE  University of Bonn$$x0
000282330 7001_ $$0P:(DE-2719)9002176$$aMantey, Richard$$b1
000282330 7001_ $$0P:(DE-HGF)0$$aGuo, Hengyuan$$b2
000282330 7001_ $$0P:(DE-2719)9003532$$aSidky, Ahmed Mokhtar$$b3
000282330 7001_ $$0P:(DE-2719)9002791$$aTouhidinia, Maryam$$b4
000282330 7001_ $$0P:(DE-2719)9003488$$aButt, Tanzeem$$b5
000282330 7001_ $$0P:(DE-2719)9002351$$aSobhani, Roohollah$$b6
000282330 7001_ $$0P:(DE-2719)2812449$$aEstrada, Santiago$$b7
000282330 7001_ $$0P:(DE-2719)2812735$$aHaendler, Kristian$$b8
000282330 7001_ $$0P:(DE-HGF)0$$aZhao, Shixiao$$b9
000282330 7001_ $$0P:(DE-HGF)0$$aShang, Xuequn$$b10
000282330 7001_ $$0P:(DE-2719)9000846$$aDe Domenico, Elena$$b11
000282330 7001_ $$0P:(DE-2719)2812219$$aBeyer, Marc D.$$b12
000282330 7001_ $$0P:(DE-2719)2810403$$aBreteler, Monique M. B.$$b13
000282330 7001_ $$0P:(DE-2719)2812578$$aAziz, N. Ahmad$$b14$$eLast author
000282330 773__ $$a10.1101/2025.11.13.25340159
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000282330 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a School of Computer Science, Northwestern Polytechnical University, Xi’an, China$$b2
000282330 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9003532$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b3$$kDZNE
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000282330 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a School of Computer Science, Northwestern Polytechnical University, Xi’an, China$$b9
000282330 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a School of Computer Science, Northwestern Polytechnical University, Xi’an, China$$b10
000282330 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9000846$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b11$$kDZNE
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000282330 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810403$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b13$$kDZNE
000282330 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812578$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b14$$kDZNE
000282330 9131_ $$0G:(DE-HGF)POF4-354$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Prevention and Healthy Aging$$x0
000282330 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
000282330 9141_ $$y2025
000282330 9201_ $$0I:(DE-2719)5000071$$kAG Aziz$$lPopulation & Clinical Neuroepidemiology$$x0
000282330 9201_ $$0I:(DE-2719)1012001$$kAG Breteler$$lPopulation Health Sciences$$x1
000282330 9201_ $$0I:(DE-2719)1013035$$kAG Beyer$$lImmunogenomics and Neurodegeneration$$x2
000282330 9201_ $$0I:(DE-2719)1040310$$kAG Reuter$$lArtificial Intelligence in Medicine$$x3
000282330 9201_ $$0I:(DE-2719)1013038$$kAG Schultze$$lClinical Single Cell Omics (CSCO) / Systems Medicine$$x4
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