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Biological constraints on GWAS SNPs at suggestive significance thresholds reveal true BMI loci [hMSC_adipocytes_captureC]

ABSTRACT: Biological constraints on GWAS SNPs at suggestive significance thresholds reveal true BMI loci [hMSC_adipocytes_captureC]

PROVIDER: PRJNA692438 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13443680.fastq.gz	Fastqsanger.gz
	SRR13443681.fastq.gz	Fastqsanger.gz
	SRR13443682.fastq.gz	Fastqsanger.gz

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Biological constraints on GWAS SNPs at suggestive significance thresholds reveal true BMI loci.

Project description:Biological constraints on GWAS SNPs at suggestive significance thresholds reveal true BMI loci.

| PRJNA692436 | ENA

Biological constraints on GWAS SNPs at suggestive significance thresholds reveal true BMI loci [hMSC_adipocytes_atacseq]

Project description:Biological constraints on GWAS SNPs at suggestive significance thresholds reveal true BMI loci [hMSC_adipocytes_atacseq]

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Biological constraints on GWAS SNPs at suggestive significance thresholds reveal true BMI loci [hMSC_adipocytes_captureC]

Project description:We investigated whether intersecting functional genomic data (ATAC-seq + promoter focused Capture C) with increasingly powered publically available GWAS for Body Mass Index and Waist to Hip Ratio could identify additional true postiive subsignficant signals (5x10-8< P value < 5x10-4) without increasing the GWAS sample size

2021-01-16 | GSE164911 | GEO

Biological constraints on GWAS SNPs at suggestive significance thresholds reveal true BMI loci [hMSC_adipocytes_atacseq]

2021-01-16 | GSE164745 | GEO

Biological constraints on GWAS SNPs at suggestive significance thresholds reveal true BMI loci.

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-01-15 | GSE164912 | GEO

Biological constraints on GWAS SNPs at suggestive significance thresholds reveal additional BMI loci.

Project description:To uncover novel significant association signals (p<5×10-8), genome-wide association studies (GWAS) requires increasingly larger sample sizes to overcome statistical correction for multiple testing. As an alternative, we aimed to identify associations among suggestive signals (5 × 10-8≤p<5×10-4) in increasingly powered GWAS efforts using chromatin accessibility and direct contact with gene promoters as biological constraints. We conducted retrospective analyses of three GIANT BMI GWAS efforts using ATAC-seq and promoter-focused Capture C data from human adipocytes and embryonic stem cell (ESC)-derived hypothalamic-like neurons. This approach, with its extremely low false-positive rate, identified 15 loci at p<5×10-5 in the 2010 GWAS, of which 13 achieved genome-wide significance by 2018, including at NAV1, MTIF3, and ADCY3. Eighty percent of constrained 2015 loci achieved genome-wide significance in 2018. We observed similar results in waist-to-hip ratio analyses. In conclusion, biological constraints on sub-significant GWAS signals can reveal potentially true-positive loci for further investigation in existing data sets without increasing sample size.

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True mangrove rhizospheres

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BMI-1 promotes Ewing sarcoma tumorigenicity independent of CDKN2a-repression

Project description:Over-expression of the polycomb group gene BMI-1 is implicated in the pathogenesis of many human cancers. In this study, we investigate the role of BMI-1 as a functional oncogene in the Ewing’s Sarcoma Family of Tumors (ESFT), a highly aggressive group of bone and soft tissue tumors. Our data show that BMI-1 is highly expressed by the majority of primary ESFT and ESFT cell lines. However, in contrast to previous reports in other human cancer cell types, knockdown of BMI-1 in ESFT cell lines has no effect on cell survival. Instead, gain and loss of function studies in vitro and in vivo demonstrate that BMI-1 promotes the anchorage independent growth and tumorigenicity of ESFT. Importantly, we also find that modulation of BMI-1 alters the tumorigenicity of both p16-wild type and p16-null cell lines and that BMI-1-mediated effects on growth promotion are independent of CDKN2a repression. Gene expression profiling of ESFT cells following BMI-1 modulation reveals novel downstream effectors of BMI-1 function including key developmental, cell:cell and cell:matrix adhesion pathways. These data support a central role for BMI-1 in the pathogenesis of ESFT and reveal that p16-independent functions of BMI-1 are largely responsible for its oncogenic function in this tumor family. Keywords: Modification of BMI-1 expression in ESFT cell lines

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Project description:We measured genes expression differences in antibody secreting cells from LynKO mice in following treatment with a BMI-1 inhibitor (PTC-028) or a vehicle control. BMI-1 inhibition lead to a reduction in antibody secreting cells in LynKO mice and in humans donors. We performed RNA sequencing to understand the impact of BMI-1 inhibition on antibody secreting cells in LynKO mice.

2023-10-05 | GSE239515 | GEO

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