Expression quantitative trait loci-derived scores and white matter microstructure in UK Biobank: a novel approach to integrating genetics and neuroimaging

被引：8

作者：

Barbu, Miruna C. ^{[1
]}

Spiliopoulou, Athina ^{[2
,3
]}

Colombo, Marco ^{[2
]}

McKeigue, Paul ^{[2
]}

Clarke, Toni-Kim ^{[1
]}

Howard, David M. ^{[1
,4
]}

Adams, Mark J. ^{[1
]}

Shen, Xueyi ^{[1
]}

Lawrie, Stephen M. ^{[1
]}

McIntosh, Andrew M. ^{[1
,5
]}

Whalley, Heather C. ^{[1
]}

机构：

[1] Univ Edinburgh, Ctr Clin Brain Sci, Div Psychiat, Edinburgh, Midlothian, Scotland

[2] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland

[3] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland

[4] Kings Coll London, Social Genet & Dev Psychiat Ctr, Inst Psychiat Psychol & Neurosci, London, England

[5] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Sch Philosophy Psychol & Language Sci, Edinburgh, Midlothian, Scotland

来源：

TRANSLATIONAL PSYCHIATRY | 2020年 / 10卷 / 01期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

MESSENGER-RNA EXPRESSION; NEURONAL DIFFERENTIATION; N-MYRISTOYLTRANSFERASE; FRACTIONAL ANISOTROPY; HUMAN BRAIN; GWAS; HERITABILITY; PRODYNORPHIN; DEPRESSION; ETIOLOGY;

D O I：

10.1038/s41398-020-0724-y

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

Expression quantitative trait loci (eQTL) are genetic variants associated with gene expression. Using genome-wide genotype data, it is now possible to impute gene expression using eQTL mapping efforts. This approach can be used to analyse previously unexplored relationships between gene expression and heritable in vivo measures of human brain structural connectivity. Using large-scale eQTL mapping studies, we computed 6457 gene expression scores (eQTL scores) using genome-wide genotype data in UK Biobank, where each score represents a genetic proxy measure of gene expression. These scores were then tested for associations with two diffusion tensor imaging measures, fractional anisotropy (N-FA = 14,518) and mean diffusivity (N-MD = 14,485), representing white matter structural integrity. We found FDR-corrected significant associations between 8 eQTL scores and structural connectivity phenotypes, including global and regional measures (beta(absolute) FA = 0.0339-0.0453; MD = 0.0308-0.0381) and individual tracts (beta(absolute) FA = 0.0320-0.0561; MD = 0.0295-0.0480). The loci within these eQTL scores have been reported to regulate expression of genes involved in various brain-related processes and disorders, such as neurite outgrowth and Parkinson's disease (DCAKD, SLC35A4, SEC14L4, SRA1, NMT1, CPNE1, PLEKHM1, UBE3C). Our findings indicate that eQTL scores are associated with measures of in vivo brain connectivity and provide novel information not previously found by conventional genome-wide association studies. Although the role of expression of these genes regarding white matter microstructural integrity is not yet clear, these results suggest it may be possible, in future, to map potential trait- and disease-associated eQTL to in vivo brain connectivity and better understand the mechanisms of psychiatric disorders and brain traits, and their associated imaging findings.

引用

页数：12

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