GCTA: A Tool for Genome-wide Complex Trait Analysis

Yang, Jian; Lee, Sang; Goddard, Michael E.; Visscher, Peter M.

doi:10.1016/j.ajhg.2010.11.011

Cited by 6,724 publications

(7,503 citation statements)

References 31 publications

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“…The analysis of secondary signals in the NUBP2 locus was performed using the software gcta (Yang et al ., 2011) and the genotypes of the SHIP cohort as a reference, and was verified by an analysis using the genotypes of the NHS/HPFS cohorts as a reference.…”

Section: Methodsmentioning

confidence: 99%

Genomewide meta‐analysis identifies loci associated with IGF ‐I and IGFBP ‐3 levels with impact on age‐related traits

Teumer¹,

Qi²,

Nethander³

et al. 2016

Aging Cell

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SummaryThe growth hormone/insulin‐like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF‐related proteins including IGF‐I and IGF‐binding protein‐3 (IGFBP‐3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30 884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF‐I and IGFBP‐3 concentrations (IGF1, IGFBP3,GCKR,TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype–phenotype associations between men and women, were found only for associations of IGFBP‐3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF‐I and IGFBP‐3 concentrations. The IGF‐I‐decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90 years. The known longevity‐associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF‐I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF‐I‐ and IGFBP‐3‐associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF‐I and IGFBP‐3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity‐associated loci.

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Section: Methodsmentioning

confidence: 99%

Genomewide meta‐analysis identifies loci associated with IGF ‐I and IGFBP ‐3 levels with impact on age‐related traits

Teumer¹,

Qi²,

Nethander³

et al. 2016

Aging Cell

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“…Association testing between phenotypic outcomes and imputed genotype allelic dosages was performed by linear regression under an additive genetic model using SNPTESTv2 [Marchini J and Howie B 2010], adjusting for age, years of education, and the first principal component. Genome‐wide Complex Trait Analysis (GCTA) software which implements a restricted maximum likelihood (REML) analysis was used to estimate the proportion of phenotypic variance explained by all genome‐wide SNPs (SNP‐heritability) [Yang J et al, 2011]. We tested for correlations between phenotypes and polygenic risk scores by linear regression in R (http://www.r-project.org/), utilizing the same covariates as above.…”

Section: Methodsmentioning

confidence: 99%

Common genetic variation and schizophrenia polygenic risk influence neurocognitive performance in young adulthood

Hatzimanolis

Bhatnagar

Moes

et al. 2015

American J of Med Genetics Pt B

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Neurocognitive abilities constitute complex traits with considerable heritability. Impaired neurocognition is typically observed in schizophrenia (SZ), whereas convergent evidence has shown shared genetic determinants between neurocognition and SZ. Here, we report a genome‐wide association study (GWAS) on neuropsychological and oculomotor traits, linked to SZ, in a general population sample of healthy young males (n = 1079). Follow‐up genotyping was performed in an identically phenotyped internal sample (n = 738) and an independent cohort of young males with comparable neuropsychological measures (n = 825). Heritability estimates were determined based on genome‐wide single‐nucleotide polymorphisms (SNPs) and potential regulatory effects on gene expression were assessed in human brain. Correlations with general cognitive ability and SZ risk polygenic scores were tested utilizing meta‐analysis GWAS results by the Cognitive Genomics Consortium (COGENT) and the Psychiatric Genomics Consortium (PGC‐SZ). The GWAS results implicated biologically relevant genetic loci encoding protein targets involved in synaptic neurotransmission, although no robust individual replication was detected and thus additional validation is required. Secondary permutation‐based analysis revealed an excess of strongly associated loci among GWAS top‐ranked signals for verbal working memory (WM) and antisaccade intra‐subject reaction time variability (empirical P < 0.001), suggesting multiple true‐positive single‐SNP associations. Substantial heritability was observed for WM performance. Further, sustained attention/vigilance and WM were suggestively correlated with both COGENT and PGC‐SZ derived polygenic scores. Overall, these results imply that common genetic variation explains some of the variability in neurocognitive functioning among young adults, particularly WM, and provide supportive evidence that increased SZ genetic risk predicts neurocognitive fluctuations in the general population. © 2015 The Authors American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

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“…It is arguably more important in ecological and conservation genetics to understand the heritability of a trait than to identify some of the loci responsible for heritable variation in the trait, as it is the heritability of a trait that determines the magnitude of the expected response to selection. The additive genetic variance and heritability can readily be estimated using linear mixed effects models (Rönnegård et al., 2016; Santure et al., 2013; Yang, Lee, Goddard, & Visscher, 2011) in GWAS, even in cases where no individual loci pass the stringent thresholds of statistical significance. In addition, heritability can be partitioned among chromosomes to determine whether the trait of interest is likely to be polygenic (i.e., affected by a very large number of loci), in which case chromosome‐specific heritability is expected to increase with the number of genes on a chromosome (Santure et al., 2013).…”

Section: Improving Downstream Computational Analysesmentioning

confidence: 99%

Recent advances in conservation and population genomics data analysis

Hendricks

Anderson

Antão

et al. 2018

Evolutionary Applications

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New computational methods and next‐generation sequencing (NGS) approaches have enabled the use of thousands or hundreds of thousands of genetic markers to address previously intractable questions. The methods and massive marker sets present both new data analysis challenges and opportunities to visualize, understand, and apply population and conservation genomic data in novel ways. The large scale and complexity of NGS data also increases the expertise and effort required to thoroughly and thoughtfully analyze and interpret data. To aid in this endeavor, a recent workshop entitled “Population Genomic Data Analysis,” also known as “ConGen 2017,” was held at the University of Montana. The ConGen workshop brought 15 instructors together with knowledge in a wide range of topics including NGS data filtering, genome assembly, genomic monitoring of effective population size, migration modeling, detecting adaptive genomic variation, genomewide association analysis, inbreeding depression, and landscape genomics. Here, we summarize the major themes of the workshop and the important take‐home points that were offered to students throughout. We emphasize increasing participation by women in population and conservation genomics as a vital step for the advancement of science. Some important themes that emerged during the workshop included the need for data visualization and its importance in finding problematic data, the effects of data filtering choices on downstream population genomic analyses, the increasing availability of whole‐genome sequencing, and the new challenges it presents. Our goal here is to help motivate and educate a worldwide audience to improve population genomic data analysis and interpretation, and thereby advance the contribution of genomics to molecular ecology, evolutionary biology, and especially to the conservation of biodiversity.

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GCTA: A Tool for Genome-wide Complex Trait Analysis

Cited by 6,724 publications

References 31 publications

Genomewide meta‐analysis identifies loci associated with IGF ‐I and IGFBP ‐3 levels with impact on age‐related traits

Genomewide meta‐analysis identifies loci associated with IGF ‐I and IGFBP ‐3 levels with impact on age‐related traits

Common genetic variation and schizophrenia polygenic risk influence neurocognitive performance in young adulthood

Recent advances in conservation and population genomics data analysis

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