MungeSumstats: a Bioconductor package for the standardization and quality control of many GWAS summary statistics

Murphy, Alan E; Schilder, Brian M; Skene, Nathan G.

doi:10.1093/bioinformatics/btab665

Cited by 66 publications

(49 citation statements)

References 14 publications

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“…GWAS summary statistics for AD [ 14 ] were tested for enrichment in microglial nuclei and monocytes samples using MAGMA (v1.08) [ 70 ] and MungeSumstats (v1.1.24) [ 71 ] packages [ 40 ]. First, summary statistics were mapped to genes using the map.snps.to.genes function of MAGMA.Celltyping (v1.0.1) [ 40 ].…”

Section: Methodsmentioning

confidence: 99%

Alzheimer’s disease-related transcriptional sex differences in myeloid cells

Coales

Tsartsalis

Fancy

et al. 2022

J Neuroinflammation

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Sex differences have been identified in many diseases associated with dysregulated immune responses, including Alzheimer’s disease (AD), for which approximately two-thirds of patients are women. An accumulating body of research indicates that microglia may play a causal role in the pathogenesis of this disease. We hypothesised that sex differences in the transcriptome of human myeloid cells may contribute to the sex difference observed in AD prevalence. To explore this, we assessed bulk and single-nuclear RNA sequencing data sets generated from four human derived myeloid cell populations: post-mortem microglial nuclei, peripheral monocytes, monocyte-derived macrophages (MDMs) and induced pluripotent stem cell derived microglial-like cells (MGLs). We found that expression of AD risk genes, gene signatures associated with the inflammatory response in AD, and genes related to proinflammatory immune responses were enriched in microglial nuclei isolated from aged female donors without ante-mortem neurological disease, relative to those from males. In addition, these inflammation-associated gene sets were found to be enriched in peripheral monocytes isolated from postmenopausal women and in MDMs obtained from premenopausal individuals relative to age-matched males. Expression of these gene sets did not differ in MDMs derived from women whose blood was sampled across the menstrual cycle or in MGLs cultured with 17β-oestradiol. This suggests that the observed gene set enrichments in myeloid cells from women were not being driven by acute hormonal influences. Together, these data support the hypothesis that the increased prevalence of AD in women may be partly explained by a myeloid cell phenotype biased towards expression of biological processes relevant to AD.

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Section: Methodsmentioning

confidence: 99%

Alzheimer’s disease-related transcriptional sex differences in myeloid cells

Coales

Tsartsalis

Fancy

et al. 2022

J Neuroinflammation

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“…The meta-analysis of this study consists of the three EUR participant studies: UKB-EUR+ FinMetSeq+ Kettunen et al datasets (N=114,124 to 124,024). MungeSumstats 55 was used in pre-processing to harmonize effect alleles from separate cohorts to the reference genome. UKB-EUR was used to estimate the number of effective traits for the three EUR meta-analysis cohorts.…”

Section: Methodsmentioning

confidence: 99%

“…The 1000 Genomes European set was used as the LD reference panel 50 . MungeSumstats 55 was used to harmonize alleles and convert summary statistics to LDSC format for this and subsequent steps. Variance explained was calculated by the formula (2 × MAF × (1 - MAF) × β 2 ).…”

Section: Methodsmentioning

confidence: 99%

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Fifty-one novel and replicated GWAS loci for polyunsaturated and monounsaturated fatty acids in 124,024 Europeans

Francis

Sun

et al. 2022

Preprint

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Circulating polyunsaturated and monounsaturated fatty acid (PUFA and MUFA) levels, whose imbalances co-occur with human metabolic diseases, have strong heritable components. We performed the largest genome-wide association study (GWAS) to-date on fourteen PUFA and MUFA phenotypes, measured by nuclear magnetic resonance in plasma. We identified 612 significant loci-phenotype associations (115 unique loci; P < 1.678*10−8) in a European cohort from UK Biobank (UKB-EUR; n=101,729). Replication of five phenotypes (omega-3, omega-6, DHA, LA, MUFAs) was conducted in two external European studies: FinMetSeq (n=8,751) and a meta-analysis by Kettunnen et al. (n=3,644-13,544). Meta-analysis of these three studies yielded 254 significant loci-phenotype associations (109 unique loci; P < 2.439*10−8); we identified 87 novel loci, 51 of which were replicated. A transcriptome-wide association study of the UKB-EUR cohort revealed an additional twelve novel loci. This study improves our understanding of the genetic architecture of unsaturated fatty acids, and can inform future gene-based dietary interventions.

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“…Base summary statistics were pruned with the MungeSumStats R package 66 to remove multiallelic variants, align reference alleles to build GRCh37, and adjust weights for the appropriate reference alleles. The target TANGL dataset SNPs were also filtered to keep only bi-allelic variants and aligned to the same reference using PLINK v2.0.…”

Section: Methodsmentioning

confidence: 99%

Multi-ancestry meta-analysis and fine-mapping in Alzheimer’s Disease

Lake

Makarious

Kim

et al. 2022

Preprint

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Genome-wide association studies (GWAS) of Alzheimer's disease are predominantly carried out in European ancestry individuals despite the known variation in genetic architecture and disease prevalence across global populations. We leveraged published and de novo GWAS from European, East Asian, African American, and Caribbean Hispanic populations to perform the largest multi-ancestry GWAS meta-analysis of Alzheimer's disease to date. This method allowed us to identify two independent novel disease-associated loci on chromosome 3. We also leveraged diverse haplotype structures to fine-map nine loci and globally assessed the heterogeneity of known risk factors across populations. Additionally we compared the generalizability of multi-ancestry- and single-ancestry-derived polygenic risk scores in a three-way admixed Colombian population. Our findings highlight the importance of multi-ancestry representation in uncovering and understanding putative factors that contribute to Alzheimer's disease risk.

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MungeSumstats: a Bioconductor package for the standardization and quality control of many GWAS summary statistics

Cited by 66 publications

References 14 publications

Alzheimer’s disease-related transcriptional sex differences in myeloid cells

Alzheimer’s disease-related transcriptional sex differences in myeloid cells

Fifty-one novel and replicated GWAS loci for polyunsaturated and monounsaturated fatty acids in 124,024 Europeans

Multi-ancestry meta-analysis and fine-mapping in Alzheimer’s Disease

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