Quality control, imputation and analysis of genome-wide genotyping data from the Illumina HumanCoreExome microarray

Coleman, Jonathan R. I.; Euesden, Jack; Patel, Hamel; Folarin, Amos; Newhouse, Stephen; Breen, Gerome

doi:10.1093/bfgp/elv037

Cited by 72 publications

(74 citation statements)

References 33 publications

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“…All participants were genotyped on the Psych Chip (Illumina Infinium PsychArray-24). Data quality was controlled in PLINK v1.07 (Purcell et al, 2007) using the same parameters as described in Coleman et al (2016). SNPs were excluded when missingness > 1%, minor allele frequency (MAF) < 0.01 or Hardy-Weinberg equilibrium (HWE) < 0.00001 and participants were excluded when missingness > 1%.…”

Section: Methodsmentioning

confidence: 99%

The polygenic risk for bipolar disorder influences brain regional function relating to visual and default state processing of emotional information

Dima

Jong

Breen

et al. 2016

NeuroImage: Clinical

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Genome-wise association studies have identified a number of common single-nucleotide polymorphisms (SNPs), each of small effect, associated with risk to bipolar disorder (BD). Several risk-conferring SNPs have been individually shown to influence regional brain activation thus linking genetic risk for BD to altered brain function. The current study examined whether the polygenic risk score method, which models the cumulative load of all known risk-conferring SNPs, may be useful in the identification of brain regions whose function may be related to the polygenic architecture of BD. We calculated the individual polygenic risk score for BD (PGR-BD) in forty-one patients with the disorder, twenty-five unaffected first-degree relatives and forty-six unrelated healthy controls using the most recent Psychiatric Genomics Consortium data. Functional magnetic resonance imaging was used to define task-related brain activation patterns in response to facial affect and working memory processing. We found significant effects of the PGR-BD score on task-related activation irrespective of diagnostic group. There was a negative association between the PGR-BD score and activation in the visual association cortex during facial affect processing. In contrast, the PGR-BD score was associated with failure to deactivate the ventromedial prefrontal region of the default mode network during working memory processing. These results are consistent with the threshold-liability model of BD, and demonstrate the usefulness of the PGR-BD score in identifying brain functional alternations associated with vulnerability to BD. Additionally, our findings suggest that the polygenic architecture of BD is not regionally confined but impacts on the task-dependent recruitment of multiple brain regions.

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Section: Methodsmentioning

confidence: 99%

The polygenic risk for bipolar disorder influences brain regional function relating to visual and default state processing of emotional information

Dima

Jong

Breen

et al. 2016

NeuroImage: Clinical

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“…The cohorts were subject to quality control and imputation separately, as described in Coleman et al [24]. In short, the data was filtered to ensure a minor allele frequency of greater than 5% for all SNPs before removal of rare variants and subjects with high levels of missing data.…”

Section: Methodsmentioning

confidence: 99%

Genetic Risk as a Marker of Amyloid-β and Tau Burden in Cerebrospinal Fluid

Patel

Folarin

Newhouse

et al. 2016

JAD

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Background: The search for a biomarker of Alzheimer’s disease (AD) pathology (amyloid-β (Aβ) and tau) is ongoing, with the best markers currently being measurements of Aβ and tau in cerebrospinal fluid (CSF) and via positron emission tomography (PET) scanning. These methods are relatively invasive, costly, and often have high screening failure rates. Consequently, research is aiming to elucidate blood biomarkers of Aβ and tau.Objective: This study aims to investigate a case/control polygenic risk score (PGRS) as a marker of tau and investigate blood markers of a combined Aβ and tau outcome for the first time. A sub-study also considers plasma tau as markers of Aβ and tau pathology in CSF.Methods: We used data from the EDAR*, DESCRIPA**, and Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohorts in a logistic regression analysis to investigate blood markers of Aβ and tau in CSF. In particular, we investigated the extent to which a case/control PGRS is predictive of CSF tau, CSF amyloid, and a combined amyloid and tau outcome. The predictive ability of models was compared to that of age, gender, and APOE genotype (‘basic model’).Results: In EDAR and DESCRIPA test data, inclusion of a case/control PGRS was no more predictive of Aβ, and a combined Aβ and tau endpoint than the basic models (accuracies of 66.0%, and 73.3% respectively). The tau model saw a small increase in accuracy compared to basic models (59.6%). ADNI 2 test data also showed a slight increase in accuracy for the Aβ model when compared to the basic models (61.4%).Conclusion: We see some evidence that a case/control PGRS is marginally more predictive of Aβ and tau pathology than the basic models. The search for predictive factors of Aβ and tau pathologies, above and beyond demographic information, is still ongoing. Better understanding of AD risk alleles, development of more sensitive assays, and studies of larger sample size are three avenues that may provide such factors. However, the clinical utility of possible predictors of brain Aβ and tau pathologies must also be investigated.*‘Beta amyloid oligomers in the early diagnosis of AD and as marker for treatment response’**‘Development of screening guidelines and criteria for pre-dementia Alzheimer’s disease’

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“…Data quality was controlled in PLINK v1.07 (Purcell et al, 2007) using the same parameters as described in Coleman et al (2016) and Dima, de Jong, Breen, and Frangou (2016). Data quality was controlled in PLINK v1.07 (Purcell et al, 2007) using the same parameters as described in Coleman et al (2016) and Dima, de Jong, Breen, and Frangou (2016).…”

Section: Polygenic Risk Score Telomere Length (Prs-tl) Constructionmentioning

confidence: 99%

“…DNA extracted from buccal swabs was genotyped on the Psych Chip (Illumina Infinium PsychArray-24). Data quality was controlled in PLINK v1.07 (Purcell et al, 2007) using the same parameters as described in Coleman et al (2016) and Dima, de Jong, Breen, and Frangou (2016). To generate polygenic risk scores for telomere length (PRS-TL), we obtained the genome-wide association study (GWAS) summary statistics from the largest TL GWAS to-date (Codd et al, 2013).…”

Section: Polygenic Risk Score Telomere Length (Prs-tl) Constructionmentioning

confidence: 99%

Telomere length as a predictor of emotional processing in the brain

Powell

Jong

Breen

et al. 2018

Human Brain Mapping

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Shorter telomere length (TL) has been associated with the development of mood disorders as well as abnormalities in brain morphology. However, so far, no studies have considered the role TL may have on brain function during tasks relevant to mood disorders. In this study, we examine the relationship between TL and functional brain activation and connectivity, while participants (n = 112) perform a functional magnetic resonance imaging (fMRI) facial affect recognition task. Additionally, because variation in TL has a substantial genetic component we calculated polygenic risk scores for TL to test if they predict face‐related functional brain activation. First, our results showed that TL was positively associated with increased activation in the amygdala and cuneus, as well as increased connectivity from posterior regions of the face network to the ventral prefrontal cortex. Second, polygenic risk scores for TL show a positive association with medial prefrontal cortex activation. The data support the view that TL and genetic loading for shorter telomeres, influence the function of brain regions known to be involved in emotional processing.

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Quality control, imputation and analysis of genome-wide genotyping data from the Illumina HumanCoreExome microarray

Cited by 72 publications

References 33 publications

The polygenic risk for bipolar disorder influences brain regional function relating to visual and default state processing of emotional information

The polygenic risk for bipolar disorder influences brain regional function relating to visual and default state processing of emotional information

Genetic Risk as a Marker of Amyloid-β and Tau Burden in Cerebrospinal Fluid

Telomere length as a predictor of emotional processing in the brain

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