Alzheimer's disease risk SNPs show no strong effect on miRNA expression in human lymphoblastoid cell lines

Inken Wohlers; Colin Schulz; Fabian Kilpert; Lars Bertram

doi:10.1016/j.neurobiolaging.2019.08.013

Alzheimer's disease risk SNPs show no strong effect on miRNA expression in human lymphoblastoid cell lines

Inken Wohlers, Colin Schulz, Fabian Kilpert, Lars Bertram^*

^*Korrespondierende/r Autor/-in für diese Arbeit

2 Zitate (Scopus)

Abstract

The role of microRNAs (miRNAs) in the pathogenesis of Alzheimer's disease (AD) is currently extensively investigated. In this study, we assessed the potential impact of AD genetic risk variants on miRNA expression by performing large-scale bioinformatic data integration. Our analysis was based on genetic variants from 3 AD genome-wide association studies (GWASs). Association with miRNA expression was tested by expression quantitative trait locus analysis using next-generation miRNA sequencing data generated in lymphoblastoid cell lines. Although, overall, we did not identify a strong effect of AD GWAS variants on miRNA expression in this cell type, we highlight 2 notable outliers, that is, miR-29c-5p and miR-6840-5p. MiR-29c-5p was recently reported to be involved in the regulation of BACE1 and SORL1 expression. In conclusion, despite 2 exceptions, our large-scale assessment provides only limited support for the hypothesis that AD GWAS variants act as miRNA expression quantitative trait loci.

Originalsprache	Englisch
Zeitschrift	Neurobiology of Aging
Jahrgang	86
Seiten (von - bis)	202.e1-202.e3
ISSN	0197-4580
DOIs	https://doi.org/10.1016/j.neurobiolaging.2019.08.013
Publikationsstatus	Veröffentlicht - 02.2020

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Computational support was provided by the OMICS compute cluster at the University of Lübeck. The authors thank Dr. Chun for help with JLIM, Dr. Gusev for help with TWAS/FUSION, and Dr. Lill for advice on implementing the ADmiReQTL workflow. Funding was provided by Peter und Traudl Engelhorn Foundation (to IW), by the European Medical Information Framework–Alzheimer’s Disease (EMIF-AD) [grant number 115372 ] (to LB), and by the Deutsche Forschungsgemeinschaft (DFG) [grant number BE2287/8 - 391523883 ] (to LB). Appendix A

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Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)

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10.1016/j.neurobiolaging.2019.08.013

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@article{19f3c10b501d4b8d95a09e79a9d3627f,

title = "Alzheimer's disease risk SNPs show no strong effect on miRNA expression in human lymphoblastoid cell lines",

abstract = "The role of microRNAs (miRNAs) in the pathogenesis of Alzheimer's disease (AD) is currently extensively investigated. In this study, we assessed the potential impact of AD genetic risk variants on miRNA expression by performing large-scale bioinformatic data integration. Our analysis was based on genetic variants from 3 AD genome-wide association studies (GWASs). Association with miRNA expression was tested by expression quantitative trait locus analysis using next-generation miRNA sequencing data generated in lymphoblastoid cell lines. Although, overall, we did not identify a strong effect of AD GWAS variants on miRNA expression in this cell type, we highlight 2 notable outliers, that is, miR-29c-5p and miR-6840-5p. MiR-29c-5p was recently reported to be involved in the regulation of BACE1 and SORL1 expression. In conclusion, despite 2 exceptions, our large-scale assessment provides only limited support for the hypothesis that AD GWAS variants act as miRNA expression quantitative trait loci.",

author = "Inken Wohlers and Colin Schulz and Fabian Kilpert and Lars Bertram",

year = "2020",

month = feb,

doi = "10.1016/j.neurobiolaging.2019.08.013",

language = "English",

volume = "86",

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journal = "Neurobiology of Aging",

issn = "0197-4580",

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T1 - Alzheimer's disease risk SNPs show no strong effect on miRNA expression in human lymphoblastoid cell lines

AU - Wohlers, Inken

AU - Schulz, Colin

AU - Kilpert, Fabian

AU - Bertram, Lars

PY - 2020/2

Y1 - 2020/2

N2 - The role of microRNAs (miRNAs) in the pathogenesis of Alzheimer's disease (AD) is currently extensively investigated. In this study, we assessed the potential impact of AD genetic risk variants on miRNA expression by performing large-scale bioinformatic data integration. Our analysis was based on genetic variants from 3 AD genome-wide association studies (GWASs). Association with miRNA expression was tested by expression quantitative trait locus analysis using next-generation miRNA sequencing data generated in lymphoblastoid cell lines. Although, overall, we did not identify a strong effect of AD GWAS variants on miRNA expression in this cell type, we highlight 2 notable outliers, that is, miR-29c-5p and miR-6840-5p. MiR-29c-5p was recently reported to be involved in the regulation of BACE1 and SORL1 expression. In conclusion, despite 2 exceptions, our large-scale assessment provides only limited support for the hypothesis that AD GWAS variants act as miRNA expression quantitative trait loci.

AB - The role of microRNAs (miRNAs) in the pathogenesis of Alzheimer's disease (AD) is currently extensively investigated. In this study, we assessed the potential impact of AD genetic risk variants on miRNA expression by performing large-scale bioinformatic data integration. Our analysis was based on genetic variants from 3 AD genome-wide association studies (GWASs). Association with miRNA expression was tested by expression quantitative trait locus analysis using next-generation miRNA sequencing data generated in lymphoblastoid cell lines. Although, overall, we did not identify a strong effect of AD GWAS variants on miRNA expression in this cell type, we highlight 2 notable outliers, that is, miR-29c-5p and miR-6840-5p. MiR-29c-5p was recently reported to be involved in the regulation of BACE1 and SORL1 expression. In conclusion, despite 2 exceptions, our large-scale assessment provides only limited support for the hypothesis that AD GWAS variants act as miRNA expression quantitative trait loci.

UR - https://www.scopus.com/pages/publications/85074433351

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U2 - 10.1016/j.neurobiolaging.2019.08.013

DO - 10.1016/j.neurobiolaging.2019.08.013

M3 - Journal articles

C2 - 31685236

AN - SCOPUS:85074433351

SN - 0197-4580

VL - 86

SP - 202.e1-202.e3

JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -

Alzheimer's disease risk SNPs show no strong effect on miRNA expression in human lymphoblastoid cell lines

Abstract

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