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3 results for “mendelian randomisation”
Data from: Sleep, major depressive disorder and Alzheimer's disease: a Mendelian randomisation study
<div class="WordSection1"> <span><span>Objective</span></span> <p><span>To explore the causal relationships between sleep, major depressive disorder (MDD), and Alzheimer's disease (AD).</span></p> <span><span>Methods</span></span> <p><span>We conducted bi-directional two-sample Mendelian randomisation analyses. Genetic associations were obtained from the largest genome-wide association studies currently available in UK Biobank (N=446,118), the Psychiatric Genomics Consortium (N=18,759), and the International Genomics of Alzheimer's Project (N=63,926). We used the inverse variance weighted Mendelian randomisation method to estimate the causal effects, and the weighted median and MR-Egger for sensitivity analyses to test for pleiotropic effects. </span></p> <span><span>Results</span></span> <p><span>We found that higher risk of AD was significantly associated with being a "morning person" (odds ratio (OR)=1.01, P=0.001), shorter sleep duration (self-reported: β=-0.006, P=1.9×10<sup>-4</sup>; accelerometer-based: β=-0.015, P=6.9×10<sup>-5</sup>), less likely to report long sleep (β=-0.003, P=7.3×10<sup>-7</sup>), earlier timing of the least active 5 hours (β=-0.024, P=1.7×10<sup>-13</sup>), and a smaller number of sleep episodes (β=-0.025, P=5.7×10<sup>-14</sup>) after adjusting for multiple comparisons. We also found that higher risk of AD was associated with lower risk of insomnia (OR=0.99, P=7×10<sup>-13</sup>). However, we did not find evidence that these abnormal sleep patterns were causally related to AD or a significant causal relationship between MDD and risk of AD. </span></p> <span><span>Conclusion</span></span> <p><span>We found that AD may causally influence sleep patterns. However, we did not find evidence supporting a causal role of disturbed sleep patterns in AD or evidence for a causal relationship between MDD and AD risk.</span></p> </div> <p> </p>
Summary statistics of eQTLs obtained from single-nuclei RNA-seq in 8 major brain cell-types for mendelian randomisation
<p>This dataset contains <em>cis</em>-eQTL summary statistics for 8 brain cell-types, generated on a snRNA-seq dataset on post-mortem brains from 391 individuals (full), as well as a controls-only (subset of full, 183 individuals).</p> <p>Genotype dosage matrices were obtained with <code>SeqArray</code>, where 0 = homozygous alt, 1 = heterozygous, 2 = homozygous ref https://bioconductor.org/packages/release/bioc/manuals/SeqArray/man/SeqArray.pdf . The eQTL models as applied by <code>MatrixEQTL</code> therefore use "ref" as the effect allele (as implemented in their additive model).</p> <p>The eQTL summary statistics for within the "full" and "controls-only" dataset have been packed into <code>.tar.gz</code> files for each cell-type, where unpacking will yield summary statistics by chromosome. Each file contains the following columns;</p> <p>1. <code>SNP</code> (in rsid format)</p> <p>2. <code>gene</code> (in symbol format)</p> <p>3. <code>t.stat</code> (t-statistic as determined by MatrixEQTL)</p> <p>4. <code>p.value</code> (linear model association p-value)</p> <p>5. <code>FDR</code> (false discovery rate as determined by MatrixEQTL)</p> <p>6. <code>beta</code> (effect size / slope of the linear model)</p> <p>7. <code>chrom</code> (chromosome in "chrN" format)</p> <p>8. <code>position</code> (SNP position, hg38 build)</p> <p>9. <code>effect_allele</code> (this is the "ref" allele as described above)</p> <p>10. <code>other_allele</code> (alternate allele)</p> <p>11. <code>maf</code> (minor allele frequency, as determined by SeqArray on this dataset)</p> <p> </p> <p>In addition, single-cell expression matrices in count format are available in the <code>single-cell_data.tar</code> archive for the full 391 individuals (2,348,438 cells). This archive contains processed single-cell counts as described in our manuscript for the 4 datasets included; "BRYOIS_192" (separated into "MS" and "AD" as per their publication), "MATTHEWS", "ROCHE_MPD92" and "MRC_60". In addition, a cell-level metadata file containing covariates and cell-type labels across all datasets is included (<code>cell_level_metadata.rds</code>). Cell barcodes and individual IDs have been renamed to preserve anonymity.</p> <p> </p> <p><strong>January 2025 update: </strong>Now published at <strong><em>Nature Genetics</em></strong>. <strong>https://www.nature.com/articles/s41588-024-02050-9</strong></p> <p><strong>May 2025 update: </strong>Added the aggregated pseudo "Bulk" eQTLs as seen in Fig 1. d. </p>
Data from: Sleep, major depressive disorder and Alzheimer’s disease: a Mendelian randomisation study
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