# Latest

**URL:** https://isgw-forum.colorado.edu/latest.md

[Latest](https://isgw-forum.colorado.edu/latest.md) · [Categories](https://isgw-forum.colorado.edu/categories.md) · [Tags](https://isgw-forum.colorado.edu/tags.md)

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## [Welcome to Discourse](https://isgw-forum.colorado.edu/t/welcome-to-discourse/7)

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**Author:** [@system](https://isgw-forum.colorado.edu/u/system)\
**Replies:** 0\
**Last updated:** [January 5, 2022, 10:38pm UTC](https://isgw-forum.colorado.edu/t/welcome-to-discourse/7 "2022-01-05T22:38:38Z")

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The first paragraph of this pinned topic will be visible as a welcome message to all new visitors on your homepage. It’s important! Edit this into a brief description of your community: Who is it for? What can they fi…

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## [Cross-Ancestry eQTL](https://isgw-forum.colorado.edu/t/cross-ancestry-eqtl/922)

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**Author:** [@Ofure\_U](https://isgw-forum.colorado.edu/u/Ofure_U)\
**Replies:** 4\
**Last updated:** [July 12, 2026, 9:10pm UTC](https://isgw-forum.colorado.edu/t/cross-ancestry-eqtl/922 "2026-07-12T21:10:34Z")

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Thanks for the fantastic lectures. I had previously asked this question during the lecture but need a reiteration including helpful resources as I am new to this kind of analysis “Is it correct practice to conduct eQTL a…

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## [Palindromic SNPS](https://isgw-forum.colorado.edu/t/palindromic-snps/926)

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**Author:** [@jameeberg](https://isgw-forum.colorado.edu/u/jameeberg)\
**Replies:** 0\
**Last updated:** [July 6, 2026, 12:56pm UTC](https://isgw-forum.colorado.edu/t/palindromic-snps/926 "2026-07-06T12:56:36Z")

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Hi, All, I would like to make a note of when it is necessary to remove palindromic SNPs from analyses downstream of GWAS. For these analyses, the effect allele and reference alleles are always annotated. It seems it is…

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## [Liability scale h2 from meta-analysis data](https://isgw-forum.colorado.edu/t/liability-scale-h2-from-meta-analysis-data/835)

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**Author:** [@kristen](https://isgw-forum.colorado.edu/u/kristen)\
**Replies:** 2\
**Last updated:** [June 17, 2026, 6:09pm UTC](https://isgw-forum.colorado.edu/t/liability-scale-h2-from-meta-analysis-data/835 "2026-06-17T18:09:57Z")

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In the video on the munge() function, it was mentioned that for meta-analyses nEff needed to be calculated as the sum of nEff from each contributing sample rather than an overall nEff based on overall case/control preval…

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## [MR QC - how can strand issues for palindromic SNPs happen with modern genotyping?](https://isgw-forum.colorado.edu/t/mr-qc-how-can-strand-issues-for-palindromic-snps-happen-with-modern-genotyping/847)

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**Author:** [@kristen](https://isgw-forum.colorado.edu/u/kristen)\
**Replies:** 3\
**Last updated:** [June 16, 2026, 6:28pm UTC](https://isgw-forum.colorado.edu/t/mr-qc-how-can-strand-issues-for-palindromic-snps-happen-with-modern-genotyping/847 "2026-06-16T18:28:29Z")

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In the first video about sensitivity analysis for Mendelian Randomization, it mentions that people often exclude palindromic SNPs because of the possibility of strand issues (but that sometimes things like allele frequen…

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## [FastMAP or meta-analysing fine-mapping statistics](https://isgw-forum.colorado.edu/t/fastmap-or-meta-analysing-fine-mapping-statistics/920)

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**Author:** [@Kristien\_vdWalt](https://isgw-forum.colorado.edu/u/Kristien_vdWalt)\
**Replies:** 0\
**Last updated:** [June 12, 2026, 2:15pm UTC](https://isgw-forum.colorado.edu/t/fastmap-or-meta-analysing-fine-mapping-statistics/920 "2026-06-12T14:15:26Z")

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Hi, Thank you for the very helpful fine-mapping lectures!! I am interested in applying the FastMAP tool to combine cohort-specific fine-mapping results, but I was unable to find the tool/publication on a quick google se…

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## [PIP Thresholds](https://isgw-forum.colorado.edu/t/pip-thresholds/919)

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**Author:** [@anonymous](https://isgw-forum.colorado.edu/u/anonymous)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 10:52pm UTC](https://isgw-forum.colorado.edu/t/pip-thresholds/919 "2026-06-11T22:52:52Z")

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What is the PIP cut-off for reliable causal? Replying to “What is the PIP cut-off for reliable causal?”: 0.9 is usually people use, which basically translates to: 10% of the variants with PIP\>0.9 are expected to be f…

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## [Fine-Mapping Window Size](https://isgw-forum.colorado.edu/t/fine-mapping-window-size/917)

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**Author:** [@anonymous](https://isgw-forum.colorado.edu/u/anonymous)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 10:50pm UTC](https://isgw-forum.colorado.edu/t/fine-mapping-window-size/917 "2026-06-11T22:50:46Z")

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In the prerecorded videos Ran suggested using a 3MB window around the lead variant, but I’ve also seen pipelines use 1Mb or even 500kb. How should we think about what window size is best to use? Replying to “In the pre…

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## [Computing In-Sample LD for Large Cohorts](https://isgw-forum.colorado.edu/t/computing-in-sample-ld-for-large-cohorts/916)

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**Author:** [@anonymous](https://isgw-forum.colorado.edu/u/anonymous)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 10:50pm UTC](https://isgw-forum.colorado.edu/t/computing-in-sample-ld-for-large-cohorts/916 "2026-06-11T22:50:10Z")

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What is the best approach for computing in-sample LD for a larger cohort (+100.000), without it being very computationally intensive? Replying to “What is the best approach for computing in-sample …”: Great question …

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## [Non-Additive Effects, cis-QTLs, and trans-QTLs](https://isgw-forum.colorado.edu/t/non-additive-effects-cis-qtls-and-trans-qtls/915)

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**Author:** [@anonymous](https://isgw-forum.colorado.edu/u/anonymous)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 10:49pm UTC](https://isgw-forum.colorado.edu/t/non-additive-effects-cis-qtls-and-trans-qtls/915 "2026-06-11T22:49:38Z")

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I was wondering if you could go over how we define the types of effects we expect. More concretely (And I don’t have a good biological rationale for this) would we expect different types of effect - i.e. trans QTL having…

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## [Credible Sets and Number of Causal Variants](https://isgw-forum.colorado.edu/t/credible-sets-and-number-of-causal-variants/913)

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**Author:** [@anonymous](https://isgw-forum.colorado.edu/u/anonymous)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 10:49pm UTC](https://isgw-forum.colorado.edu/t/credible-sets-and-number-of-causal-variants/913 "2026-06-11T22:49:02Z")

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How do you decide how many SNPs to allow in your credible set? I see that we can manual set that # Replying to “How do you decide how many SNPs to allow in your c…”: You may be looking at the number of causal variant…

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## [External LD Matrices and Fine-Mapping](https://isgw-forum.colorado.edu/t/external-ld-matrices-and-fine-mapping/912)

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**Author:** [@anonymous](https://isgw-forum.colorado.edu/u/anonymous)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 10:47pm UTC](https://isgw-forum.colorado.edu/t/external-ld-matrices-and-fine-mapping/912 "2026-06-11T22:47:12Z")

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If you don’t have access to the within-sample LD matrix (e.g., using 23andMe sum stats), how can you control for false positives generated by using an external LD matrix. For example: European 23andMe GWAS sum stats L…

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## [Minor Alleles, QQ Plots, and Practical Answers](https://isgw-forum.colorado.edu/t/minor-alleles-qq-plots-and-practical-answers/911)

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**Author:** [@anonymous](https://isgw-forum.colorado.edu/u/anonymous)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 10:46pm UTC](https://isgw-forum.colorado.edu/t/minor-alleles-qq-plots-and-practical-answers/911 "2026-06-11T22:46:39Z")

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Two questions: I noticed males were coded as 0 and females were coded a 1. Isn’t this opposite of the most frequent way this is coded? Is the answer for Q14 also incorrect? the answer is listed as 4,189,956 cis, 35,789…

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## [Functional Annotation of Highly Correlated Traits](https://isgw-forum.colorado.edu/t/functional-annotation-of-highly-correlated-traits/910)

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**Author:** [@anonymous](https://isgw-forum.colorado.edu/u/anonymous)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 10:45pm UTC](https://isgw-forum.colorado.edu/t/functional-annotation-of-highly-correlated-traits/910 "2026-06-11T22:45:29Z")

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If you have a genetic correlation between two traits (let’s say 0.9) that have a strong correlation from LDSC regression - is it possible and worth doing functional annotation of these traits to see if they differ biolog…

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## [Environmental Effects and G×E in QTL Analyses](https://isgw-forum.colorado.edu/t/environmental-effects-and-gxe-in-qtl-analyses/909)

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**Author:** [@anonymous](https://isgw-forum.colorado.edu/u/anonymous)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 10:44pm UTC](https://isgw-forum.colorado.edu/t/environmental-effects-and-gxe-in-qtl-analyses/909 "2026-06-11T22:44:57Z")

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how do we model environmental effects or gene–environment interactions in the QTL analyses, it is the same as looking into key covariates such as age, sex, ancestry principal components , thank Replying to “how do we m…

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## [Multi-cohort fine mapping approach](https://isgw-forum.colorado.edu/t/multi-cohort-fine-mapping-approach/908)

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**Author:** [@helenl](https://isgw-forum.colorado.edu/u/helenl)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 9:01pm UTC](https://isgw-forum.colorado.edu/t/multi-cohort-fine-mapping-approach/908 "2026-06-11T21:01:02Z")

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Question about multi-cohort fine mapping as taught at the end of the video on Statistical fine-mapping part 2: would a joint modeling approach be expected to be more accurate than the combining approach, and if so, why? …

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## [Weighted Mode Estimates](https://isgw-forum.colorado.edu/t/weighted-mode-estimates/907)

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**Author:** [@anonymous](https://isgw-forum.colorado.edu/u/anonymous)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 4:06pm UTC](https://isgw-forum.colorado.edu/t/weighted-mode-estimates/907 "2026-06-11T16:06:09Z")

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How was that weighted mode estimate picked from all the other estimates that the function output? Smallest standard error? Replying to “How was that weighted mode estimate picked from al…”: Sorry I understand what yo…

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## [MR Across Ancestries](https://isgw-forum.colorado.edu/t/mr-across-ancestries/905)

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**Author:** [@anonymous](https://isgw-forum.colorado.edu/u/anonymous)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 4:05pm UTC](https://isgw-forum.colorado.edu/t/mr-across-ancestries/905 "2026-06-11T16:05:35Z")

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do MR results translate well to other ancestries? is there a way to avaluate that? https://www.researchsquare.com/article/rs-6091701/v1 Replying to “do MR results translate well to other ancestries? …”: In general, …

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## [Exposure Strength and Instrument Quality](https://isgw-forum.colorado.edu/t/exposure-strength-and-instrument-quality/904)

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**Author:** [@anonymous](https://isgw-forum.colorado.edu/u/anonymous)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 4:04pm UTC](https://isgw-forum.colorado.edu/t/exposure-strength-and-instrument-quality/904 "2026-06-11T16:04:47Z")

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Is there a certain minimum SNP heritabilty required for the exposure? Or minimum VAF for a SNP? Replying to “Is there a certain minimum SNP heritabilty require…”: The strength of the exposure-SNP association the key …

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## [InSIDE Assumption](https://isgw-forum.colorado.edu/t/inside-assumption/903)

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**Author:** [@anonymous](https://isgw-forum.colorado.edu/u/anonymous)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 4:03pm UTC](https://isgw-forum.colorado.edu/t/inside-assumption/903 "2026-06-11T16:03:26Z")

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is there a test to see if the InSIDE assumption holds? If the assumption is that the SNP-exposure effects aren’t correlated with the SNP-outcome effects can’t we just test that empirically? Replying to “is there a test…

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## [Wald Ratio P-values and Standard Errors](https://isgw-forum.colorado.edu/t/wald-ratio-p-values-and-standard-errors/901)

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**Author:** [@anonymous](https://isgw-forum.colorado.edu/u/anonymous)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 4:02pm UTC](https://isgw-forum.colorado.edu/t/wald-ratio-p-values-and-standard-errors/901 "2026-06-11T16:02:53Z")

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I might miss something but how to get p value and SE for a Wald ratio (Q9) Replying to “I might miss something but how to get p value and …”: beta/SE ~ Z(0,1) Replying to “I might miss something but how to get p va…

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## [Requirements for MR Exposures](https://isgw-forum.colorado.edu/t/requirements-for-mr-exposures/900)

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**Author:** [@anonymous](https://isgw-forum.colorado.edu/u/anonymous)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 4:02pm UTC](https://isgw-forum.colorado.edu/t/requirements-for-mr-exposures/900 "2026-06-11T16:02:21Z")

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You have reviewed the requirements for SNPs, but what are the requirements for exposures? Do they need to be certain types of traits? Replying to “You have reviewed the requirements for SNPs, but w…”: Here’s a nice a…

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## [Colocalisation vs MR-Egger Intercept](https://isgw-forum.colorado.edu/t/colocalisation-vs-mr-egger-intercept/899)

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**Author:** [@anonymous](https://isgw-forum.colorado.edu/u/anonymous)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 3:48pm UTC](https://isgw-forum.colorado.edu/t/colocalisation-vs-mr-egger-intercept/899 "2026-06-11T15:48:35Z")

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How should we interpret an MR result that shows strong colocalisation but also a significant MR-Egger intercept? Thanks. Replying to “How should we interpret an MR result that shows st…”: colocalisation suggests that…

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## [Pleiotropy and MR Assumptions](https://isgw-forum.colorado.edu/t/pleiotropy-and-mr-assumptions/898)

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**Author:** [@anonymous](https://isgw-forum.colorado.edu/u/anonymous)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 3:47pm UTC](https://isgw-forum.colorado.edu/t/pleiotropy-and-mr-assumptions/898 "2026-06-11T15:47:57Z")

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Does the pliatropy (I can’t spell) concern influence the second assumption as well (i.e. no SNP influences on confounders)? Thanks :slightly\_smiling\_face: Replying to “Does the pliatropy (I can’t spell) concern influen…

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## [MR Assumption 3 (Exclusion Restriction)](https://isgw-forum.colorado.edu/t/mr-assumption-3-exclusion-restriction/896)

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**Author:** [@anonymous](https://isgw-forum.colorado.edu/u/anonymous)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 3:47pm UTC](https://isgw-forum.colorado.edu/t/mr-assumption-3-exclusion-restriction/896 "2026-06-11T15:47:22Z")

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By third assumption, you mean SNP marginally not associated with outcome? Replying to “By third assumption, you mean SNP marginally not …”: Marginally, it is expected to be associated (via the exposure variable). But…

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## [Multiple Exposures in MR](https://isgw-forum.colorado.edu/t/multiple-exposures-in-mr/895)

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**Author:** [@anonymous](https://isgw-forum.colorado.edu/u/anonymous)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 3:46pm UTC](https://isgw-forum.colorado.edu/t/multiple-exposures-in-mr/895 "2026-06-11T15:46:04Z")

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How is it possible to model 2SMR with multiple traits or outcomes? Replying to “How is it possible to model 2SMR with multiple tra…”: If you want to include multiple exposures you can (under certain assumptions) use …

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## [Ascertainment Bias and Mendelian Randomization Assumptions](https://isgw-forum.colorado.edu/t/ascertainment-bias-and-mendelian-randomization-assumptions/894)

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**Author:** [@anonymous](https://isgw-forum.colorado.edu/u/anonymous)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 3:45pm UTC](https://isgw-forum.colorado.edu/t/ascertainment-bias-and-mendelian-randomization-assumptions/894 "2026-06-11T15:45:21Z")

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Would ascertainment bias affect the assumption of the random segregation of alleles? Replying to “Would ascertainment bias affect the assumption of …”: I would say no- ascertainment bias wouldn’t affect random segreg…

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## [Fine-mapping strategy in a difficult meta-analysis setting](https://isgw-forum.colorado.edu/t/fine-mapping-strategy-in-a-difficult-meta-analysis-setting/893)

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**Author:** [@jeongah.lee](https://isgw-forum.colorado.edu/u/jeongah.lee)\
**Replies:** 0\
**Last updated:** [June 11, 2026, 3:00pm UTC](https://isgw-forum.colorado.edu/t/fine-mapping-strategy-in-a-difficult-meta-analysis-setting/893 "2026-06-11T15:00:55Z")

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I would like to get advice on how to deal with the following scenario. Scenario I have GWAS summary statistics from a large meta-analysis of mixed-ancestry cohorts (multi-ancestry meta-GWAS). I do not have access …

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## [Random effects IVW analysis](https://isgw-forum.colorado.edu/t/random-effects-ivw-analysis/892)

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**Author:** [@bastien.rioux](https://isgw-forum.colorado.edu/u/bastien.rioux)\
**Replies:** 1\
**Last updated:** [June 11, 2026, 11:14am UTC](https://isgw-forum.colorado.edu/t/random-effects-ivw-analysis/892 "2026-06-11T11:14:58Z")

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Is there an advantage to use the random-effects version of IVW in MR? Would you use it as a primary analysis vs the fixed effect?

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## [RCode for doing biometric moderation?](https://isgw-forum.colorado.edu/t/rcode-for-doing-biometric-moderation/883)

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**Author:** [@jense180](https://isgw-forum.colorado.edu/u/jense180)\
**Replies:** 1\
**Last updated:** [June 10, 2026, 8:37pm UTC](https://isgw-forum.colorado.edu/t/rcode-for-doing-biometric-moderation/883 "2026-06-10T20:37:04Z")

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I am interested in testing whether a biometric moderation model in which genetic influences on personality vary as a function of relationship satisfaction provides a better fit to the data than a model without moderation…

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