Bayesian Genetic Colocalization Test of Two Traits Using <i>coloc</i>

Rasooly, Danielle; Peloso, Gina M.; Giambartolomei, Claudia

doi:10.1002/cpz1.627

Cited by 13 publications

(6 citation statements)

References 43 publications

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“…The merging step involved lifting over GWAS summary data to hg38 build and the removal of duplicated sites. We then estimated evidence of shared causal variants using the coloc.abf function of the coloc R package 40 . The coloc.abf estimates the posterior probabilities of 5 hypotheses including a posterior of a shared causal allele between two target traits (H4 PP), two distinct causal alleles (H3 PP), a causal allele for only one target (H1 or H2) and null of no causal allele within a locus.…”

Section: Methodsmentioning

confidence: 99%

Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry

Kamiza,

Touré,

Zhou

et al. 2023

Nat Commun

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Most genome-wide association studies (GWAS) for lipid traits focus on the separate analysis of lipid traits. Moreover, there are limited GWASs evaluating the genetic variants associated with multiple lipid traits in African ancestry. To further identify and localize loci with pleiotropic effects on lipid traits, we conducted a genome-wide meta-analysis, multi-trait analysis of GWAS (MTAG), and multi-trait fine-mapping (flashfm) in 125,000 individuals of African ancestry. Our meta-analysis and MTAG identified four and 14 novel loci associated with lipid traits, respectively. flashfm yielded an 18% mean reduction in the 99% credible set size compared to single-trait fine-mapping with JAM. Moreover, we identified more genetic variants with a posterior probability of causality >0.9 with flashfm than with JAM. In conclusion, we identified additional novel loci associated with lipid traits, and flashfm reduced the 99% credible set size to identify causal genetic variants associated with multiple lipid traits in African ancestry.

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Section: Methodsmentioning

confidence: 99%

Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry

Kamiza,

Touré,

Zhou

et al. 2023

Nat Commun

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“…In addition, colocalization analysis ( coloc package (v5.2.2) [61]) was performed for each of the model’s most important features to assess whether its methylation status and Alzheimer’s disease status share a common genetic variant. For this, the GWAS summary statistics of Alzheimer’s disease from Marioni et al (2018) [45] and the mQTL data (non-clumped cis-mQTLs, P value < 1e-5) from the GoDMC database [19] were used.…”

Section: Methodsmentioning

confidence: 99%

Blood-based multivariate methylation risk score for cognitive impairment and dementia

Koetsier,

Cavill,

Reijnders

et al. 2023

Preprint

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INTRODUCTIONGiven the established association between DNA methylation and the pathophysiology of dementia and its plausible role as a molecular mediator of lifestyle and environment, blood-derived DNA methylation data could enable early detection of dementia risk.METHODSIn conjunction with an extensive array of machine learning techniques, we employed whole blood genome-wide DNA methylation data as a surrogate for 14 modifiable and non-modifiable factors in the assessment of dementia risk in two independent cohorts of Alzheimer’s disease (AD) and Parkinson’s disease (PD).RESULTSWe established a multivariate methylation risk score (MMRS) to identify the status of mild cognitive impairment (MCI) cross-sectionally, independent of age and sex. We further demonstrated significant predictive capability of this score for the prospective onset of cognitive decline in AD and PD.DISCUSSIONOur work shows the potential of employing blood-derived DNA methylation data in the assessment of dementia risk.

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“…Then, for the signi cant CX3CL1/CX3CR1 trait having genetic correlation with PD, colocalization analysis was used to assess whether the CX3CL1/CX3CR1 trait and PD shared a causal variant in a region of the genome. Bayesian testing was used to perform colocalization analysis 25 . We used an approximation based on the minor allele frequency (MAF) of the SNP and ignored any uncertainty imputation, due to only *p* value available for our GWAS summary datasets and without regression coe cients and variances.…”

Section: Colocalization Analysismentioning

confidence: 99%

Casual association between CX3CL1/CX3CR1 and Parkinson's Disease: A Mendelian randomization and Colocalization study

Zeng,

Yusufujiang,

et al. 2024

Preprint

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Background: The association between CX3CL1/CX3CR1 and Parkinson’s Disease (PD) has been minimally explored in pre-clinical and observational studies. However, evidence from animal studies indicates that CX3CL1/CX3CR1 can exert both neuroprotective and neurotoxic effects on PD. Given the scarcity of clinical studies,our objective is to explore the causality between CX3CL1/CX3CR1 and PD using a two-sample Mendelian randomization approach in conjunction with colocalization analysis.. Methods: We constructed a bidirectional two-sample Mendelian randomization (MR) to assess the causal link between CX3CL1/CX3CR1 and PD, employing genetic variants as instrumental variables, we intend to analyze the most extensive genome-wide association study data available for PD as the outcome measure. The primary outcome was derived using the inverse variance weighted (IVW) method .Additional analyses, including Mendelian randomization Egger regression, weighted median, and mode approaches, were utilized to reinforce the robustness of our findings. The debiased inverse variance weighted estimator was introduced to adjust for potential weak instrument bias. To robustly validate our findings, we carried out a comprehensive series of sensitivity analyses. Results: Our study examined 33,674 cases of PD and 449,056 controls, revealing three key findings. We discovered that for every one-standard deviation (SD) increase in plasma CX3CR1 levels in monocytes, there was a 10.3% decrease in PD risk (IVW; OR = 0.897, 95%CI = 0.831 - 0.968, P_adj = 0.012). Furthermore, a one-SD increase in CX3CR1 levels on CD14+ CD16+ monocytes resulted in an 8.9% lower PD risk (IVW; OR = 0.911, 95% CI = 0.863 - 0.962, P_adj = 0.006), and a similar increase on CD14+ CD16- monocytes led to a 9.3% reduction in risk (IVW; OR = 0.907, 95% CI = 0.850 - 0.967, P_adj = 0.010). Through comprehensive sensitivity analyses, the reliability of these results was confirmed. Additionally, our colocalization analysis identified a significant association of the lead SNP rs6658353 with CX3CR1 expression in monocytes. This SNP also showed significant colocalization with CX3CR1 in both CD14+ CD16+ and CD14+ CD16- subsets, indicating its role in regulating CX3CR1 expression. Conclusion: This study suggests a potential link between higher peripheral expression of CX3CR1 on monocytes and a reduced risk of PD. Specifically, increased levels of plasma CX3CR1, as well as its expression on CD14+ CD16+ and CD14+ CD16- monocytes, were associated with a decreased PD risk. These results lend support to the hypothesis that CX3CR1 plays a crucial role in the causal pathway to PD.

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Bayesian Genetic Colocalization Test of Two Traits Using coloc

Cited by 13 publications

References 43 publications

Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry

Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry

Blood-based multivariate methylation risk score for cognitive impairment and dementia

Casual association between CX3CL1/CX3CR1 and Parkinson's Disease: A Mendelian randomization and Colocalization study

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