The impact of short tandem repeats on grey matter brain imaging derived phenotypes in UK Biobank

William Sproviero; Upamanyu Ghose; Laura M. Winchester; Marco Fernandes; Danielle Newby; Daisy Sproviero; Najaf Amin; Bart Smets; Karen Y. He; Ekaterina A. Khramtsova; Parth Patel; Brice A. J. Sarver; Trevor Howe; Mary Helen Black; Cornelia van Duijn; Alejo Nevado-Holgado

doi:10.1101/2023.02.27.23286496

The impact of short tandem repeats on grey matter brain imaging derived phenotypes in UK Biobank

William Sproviero^*, Upamanyu Ghose, Laura M. Winchester, Marco Fernandes, Danielle Newby, Daisy Sproviero, Najaf Amin, Bart Smets, Karen Y. He, Ekaterina A. Khramtsova, Parth Patel, Brice A. J. Sarver, Trevor Howe, Mary Helen Black, Cornelia van Duijn, Alejo Nevado-Holgado

^*Corresponding author for this work

Research output: Working paper › Preprint

Abstract

We performed a genome-wide association study of 143,067 highly polymorphic short tandem repeats (STRs) with MRI brain grey matter volumes (GMVs) on 10,702 UK Biobank (UKB) participants, including 8,751 in the discovery stage and 1,701 in the replication analysis. STRs’ repeat lengths were estimated from the UKB whole-genome sequencing data using Expansion Hunter software.

A total of 262 STRs reached genome-wide significance in the analyses of the autosomal and sex chromosomes’ (P = 6.9 × 10⁻⁸) in association with MRI -GMVs. Replication in a second batch extraction in the UKB and linkage disequilibrium (LD) analyses confirmed 12 associations of five STRs with hippocampal, intra-calcarine cortex, and cerebellum volumes with no evidence of single nucleotide polymorphisms (SNP) in LD detected in the surrounding DNA regions. Our study highlights the importance of STR variants involved in the genetic architecture of grey matter volumes.

Original language	English
Place of Publication	Online
Publisher	medRxiv
Number of pages	37
DOIs	https://doi.org/10.1101/2023.02.27.23286496
Publication status	Published - 1 Mar 2023

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Sproviero, W., Ghose, U., Winchester, L. M., Fernandes, M., Newby, D., Sproviero, D., Amin, N., Smets, B., He, K. Y., Khramtsova, E. A., Patel, P., Sarver, B. A. J., Howe, T., Black, M. H., van Duijn, C., & Nevado-Holgado, A. (2023). The impact of short tandem repeats on grey matter brain imaging derived phenotypes in UK Biobank. medRxiv. https://doi.org/10.1101/2023.02.27.23286496

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title = "The impact of short tandem repeats on grey matter brain imaging derived phenotypes in UK Biobank",

abstract = "We performed a genome-wide association study of 143,067 highly polymorphic short tandem repeats (STRs) with MRI brain grey matter volumes (GMVs) on 10,702 UK Biobank (UKB) participants, including 8,751 in the discovery stage and 1,701 in the replication analysis. STRs{\textquoteright} repeat lengths were estimated from the UKB whole-genome sequencing data using Expansion Hunter software. A total of 262 STRs reached genome-wide significance in the analyses of the autosomal and sex chromosomes{\textquoteright} (P = 6.9 × 10−8) in association with MRI -GMVs. Replication in a second batch extraction in the UKB and linkage disequilibrium (LD) analyses confirmed 12 associations of five STRs with hippocampal, intra-calcarine cortex, and cerebellum volumes with no evidence of single nucleotide polymorphisms (SNP) in LD detected in the surrounding DNA regions. Our study highlights the importance of STR variants involved in the genetic architecture of grey matter volumes.",

author = "William Sproviero and Upamanyu Ghose and Winchester, \{Laura M.\} and Marco Fernandes and Danielle Newby and Daisy Sproviero and Najaf Amin and Bart Smets and He, \{Karen Y.\} and Khramtsova, \{Ekaterina A.\} and Parth Patel and Sarver, \{Brice A. J.\} and Trevor Howe and Black, \{Mary Helen\} and \{van Duijn\}, Cornelia and Alejo Nevado-Holgado",

note = "Funding: This study was funded by Janssen Research and Development Ltd of Johnson and Johnson.",

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doi = "10.1101/2023.02.27.23286496",

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T1 - The impact of short tandem repeats on grey matter brain imaging derived phenotypes in UK Biobank

AU - Sproviero, William

AU - Ghose, Upamanyu

AU - Winchester, Laura M.

AU - Fernandes, Marco

AU - Newby, Danielle

AU - Sproviero, Daisy

AU - Amin, Najaf

AU - Smets, Bart

AU - He, Karen Y.

AU - Khramtsova, Ekaterina A.

AU - Patel, Parth

AU - Sarver, Brice A. J.

AU - Howe, Trevor

AU - Black, Mary Helen

AU - van Duijn, Cornelia

AU - Nevado-Holgado, Alejo

N1 - Funding: This study was funded by Janssen Research and Development Ltd of Johnson and Johnson.

PY - 2023/3/1

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N2 - We performed a genome-wide association study of 143,067 highly polymorphic short tandem repeats (STRs) with MRI brain grey matter volumes (GMVs) on 10,702 UK Biobank (UKB) participants, including 8,751 in the discovery stage and 1,701 in the replication analysis. STRs’ repeat lengths were estimated from the UKB whole-genome sequencing data using Expansion Hunter software. A total of 262 STRs reached genome-wide significance in the analyses of the autosomal and sex chromosomes’ (P = 6.9 × 10−8) in association with MRI -GMVs. Replication in a second batch extraction in the UKB and linkage disequilibrium (LD) analyses confirmed 12 associations of five STRs with hippocampal, intra-calcarine cortex, and cerebellum volumes with no evidence of single nucleotide polymorphisms (SNP) in LD detected in the surrounding DNA regions. Our study highlights the importance of STR variants involved in the genetic architecture of grey matter volumes.

AB - We performed a genome-wide association study of 143,067 highly polymorphic short tandem repeats (STRs) with MRI brain grey matter volumes (GMVs) on 10,702 UK Biobank (UKB) participants, including 8,751 in the discovery stage and 1,701 in the replication analysis. STRs’ repeat lengths were estimated from the UKB whole-genome sequencing data using Expansion Hunter software. A total of 262 STRs reached genome-wide significance in the analyses of the autosomal and sex chromosomes’ (P = 6.9 × 10−8) in association with MRI -GMVs. Replication in a second batch extraction in the UKB and linkage disequilibrium (LD) analyses confirmed 12 associations of five STRs with hippocampal, intra-calcarine cortex, and cerebellum volumes with no evidence of single nucleotide polymorphisms (SNP) in LD detected in the surrounding DNA regions. Our study highlights the importance of STR variants involved in the genetic architecture of grey matter volumes.

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BT - The impact of short tandem repeats on grey matter brain imaging derived phenotypes in UK Biobank

PB - medRxiv

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ER -

The impact of short tandem repeats on grey matter brain imaging derived phenotypes in UK Biobank

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