The influence of X chromosome variants on trait neuroticism.
Michelle Luciano,Gail Davies,Kim M. Summers,W. David Hill,Caroline Hayward,David C. Liewald,David J. Porteous,Catharine R. Gale,Catharine R. Gale,Andrew M. McIntosh,Ian J. Deary +10 more
TLDR
It is concluded that the X chromosome harbours significant variants influencing neuroticism, and might prove important for other quantitative traits and complex disorders.Abstract:
Autosomal variants have successfully been associated with trait neuroticism in genome-wide analysis of adequately powered samples. But such studies have so far excluded the X chromosome from analysis. Here, we report genetic association analyses of X chromosome and XY pseudoautosomal single nucleotide polymorphisms (SNPs) and trait neuroticism using UK Biobank samples (N = 405,274). Significant association was found with neuroticism on the X chromosome for 204 markers found within three independent loci (a further 783 were suggestive). Most of the lead neuroticism-related X chromosome variants were located in intergenic regions (n = 397). Involvement of HS6ST2, which has been previously associated with sociability behaviour in the dog, was supported by single SNP and gene-based tests. We found that the amino acid and nucleotide sequences are highly conserved between dogs and humans. From the suggestive X chromosome variants, there were 19 nearby genes which could be linked to gene ontology information. Molecular function was primarily related to binding and catalytic activity; notable biological processes were cellular and metabolic, and nucleic acid binding and transcription factor protein classes were most commonly involved. X-variant heritability of neuroticism was estimated at 0.22% (SE = 0.05) from a full dosage compensation model. A polygenic X-variant score created in an independent sample (maximum N ≈ 7,300) did not predict significant variance in neuroticism, psychological distress, or depressive disorder. We conclude that the X chromosome harbours significant variants influencing neuroticism, and might prove important for other quantitative traits and complex disorders.read more
Citations
More filters
Posted ContentDOI
Enhanced Brain Imaging Genetics in UK Biobank
Stephen M. Smith,Gwenaëlle Douaud,Winfield Chen,Taylor Hanayik,Fidel Alfaro-Almagro,Kevin Sharp,Lloyd T. Elliott +6 more
TL;DR: A new open resource of GWAS summary statistics, resulting from a greatly expanded set of genetic associations with brain phenotypes, using the 2020 UKB imaging data release of approximately 40,000 subjects, and includes associations on the X chromosome for the first time.
Journal ArticleDOI
Heterogeneity and Polygenicity in Psychiatric Disorders: A Genome-Wide Perspective.
TL;DR: The ways in which sex and diagnostic complexity contribute to risk locus discovery in schizophrenia, bipolar disorder, attention deficit hyperactivity disorder, autism spectrum disorder, posttraumatic stress disorder, major depressive disorder, obsessive-compulsive disorder, Tourette’s syndrome and chronic tic disorder are highlighted.
Journal ArticleDOI
MungeSumstats: A Bioconductor package for the standardisation and quality control of many GWAS summary statistics.
TL;DR: MungeSumstats as discussed by the authors is a Bioconductor R package for the standardisation and quality control of GWAS summary statistics, which can handle the most common summary statistic formats, including variant call format (VCF) producing a reformatted, standardised, tabular summary statistic file, VCF or R native data object.
Journal ArticleDOI
Joint identification of sex and sex-linked scaffolds in non-model organisms using low depth sequencing data.
TL;DR: SATC as mentioned in this paper is a method to assign sex to samples and identify sex-linked scaffolds from next generation sequencing (NGS) data using principal component analysis (PCA) and subsequent Gaussian mixture clustering.
Posted ContentDOI
MungeSumstats: A Bioconductor package for the standardisation and quality control of many GWAS summary statistics
Alan E Murphy,Nathan G. Skene +1 more
TL;DR: MungeSumstats as discussed by the authors is a Bioconductor R package for the standardisation and quality control of GWAS summary statistics, which can handle the most common summary statistic formats, including variant call format (VCF) producing a reformatted, standardised, tabular summary statistic file.
References
More filters
Journal ArticleDOI
Controlling the false discovery rate: a practical and powerful approach to multiple testing
Yoav Benjamini,Yosef Hochberg +1 more
TL;DR: In this paper, a different approach to problems of multiple significance testing is presented, which calls for controlling the expected proportion of falsely rejected hypotheses -the false discovery rate, which is equivalent to the FWER when all hypotheses are true but is smaller otherwise.
Journal ArticleDOI
PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses
Shaun Purcell,Shaun Purcell,Benjamin M. Neale,Benjamin M. Neale,Kathe Todd-Brown,Lori Thomas,Manuel A. R. Ferreira,David Bender,David Bender,Julian Maller,Julian Maller,Pamela Sklar,Pamela Sklar,Paul I.W. de Bakker,Paul I.W. de Bakker,Mark J. Daly,Mark J. Daly,Pak C. Sham +17 more
TL;DR: This work introduces PLINK, an open-source C/C++ WGAS tool set, and describes the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation, which focuses on the estimation and use of identity- by-state and identity/descent information in the context of population-based whole-genome studies.
Journal ArticleDOI
UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age
Cathie Sudlow,John Gallacher,Naomi E. Allen,Valerie Beral,Paul Burton,John Danesh,Paul Downey,Paul Elliott,Jane Green,Martin J Landray,Bette Liu,Paul M. Matthews,Giok Ong,Jill P. Pell,Alan J. Silman,Alan Young,Tim Sprosen,Tim Peakman,Rory Collins +18 more
TL;DR: The UK Biobank is described, a large population-based prospective study, established to allow investigation of the genetic and non-genetic determinants of the diseases of middle and old age.
Journal ArticleDOI
The UK Biobank resource with deep phenotyping and genomic data
Clare Bycroft,Colin Freeman,Desislava Petkova,Desislava Petkova,Gavin Band,Lloyd T. Elliott,Kevin Sharp,Allan Motyer,Damjan Vukcevic,Olivier Delaneau,Olivier Delaneau,Jared O'Connell,Adrian Cortes,Adrian Cortes,Samantha Welsh,Alan Young,Mark Effingham,Gil McVean,Stephen Leslie,Naomi E. Allen,Peter Donnelly,Jonathan Marchini +21 more
TL;DR: Deep phenotype and genome-wide genetic data from 500,000 individuals from the UK Biobank is described, describing population structure and relatedness in the cohort, and imputation to increase the number of testable variants to 96 million.
Journal ArticleDOI
METAL: fast and efficient meta-analysis of genomewide association scans.
TL;DR: METAL provides a computationally efficient tool for meta-analysis of genome-wide association scans, which is a commonly used approach for improving power complex traits gene mapping studies.