# Theory & background

**URL:** https://isgw-forum.colorado.edu/c/theory-background-computing/5.md

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## [About the Theory & background category](https://isgw-forum.colorado.edu/t/about-the-theory-background-category/12)

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**Author:** [@JML](https://isgw-forum.colorado.edu/u/JML)\
**Replies:** 1\
**Last updated:** [March 7, 2023, 6:07pm UTC](https://isgw-forum.colorado.edu/t/about-the-theory-background-category/12 "2023-03-07T18:07:45Z")

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This is for general discussion about theory (e.g., population genetics; population stratification), history of genetics and behavioral genetics, and programming (e.g., UNIX, R).

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## [Day 4 Imputation](https://isgw-forum.colorado.edu/t/day-4-imputation/798)

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**Author:** [@b.i.l.m.mendis](https://isgw-forum.colorado.edu/u/b.i.l.m.mendis)\
**Replies:** 0\
**Last updated:** [June 4, 2026, 4:02pm UTC](https://isgw-forum.colorado.edu/t/day-4-imputation/798 "2026-06-04T16:02:31Z")

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I have a question about imputation in GWAS. Since we often genotype only a subset of variants, for example around 500,000 SNPs, and then impute millions of additional variants using a reference panel, many association si…

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## [Relationship between missing heritability and measurement error](https://isgw-forum.colorado.edu/t/relationship-between-missing-heritability-and-measurement-error/753)

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**Author:** [@henrik.dobewall](https://isgw-forum.colorado.edu/u/henrik.dobewall)\
**Replies:** 2\
**Last updated:** [June 3, 2026, 10:30pm UTC](https://isgw-forum.colorado.edu/t/relationship-between-missing-heritability-and-measurement-error/753 "2026-06-03T22:30:48Z")

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When listening to todays (day 1) lectures I was wondering about the relationship between missing heritability and measurement error. Hight for instance, does not have much noise in the measurement. But most complex trait…

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## [Selective samples and GCTA](https://isgw-forum.colorado.edu/t/selective-samples-and-gcta/752)

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**Author:** [@henrik.dobewall](https://isgw-forum.colorado.edu/u/henrik.dobewall)\
**Replies:** 1\
**Last updated:** [June 3, 2026, 1:59am UTC](https://isgw-forum.colorado.edu/t/selective-samples-and-gcta/752 "2026-06-03T01:59:19Z")

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We talk about unmet assumptions like assortative mating, height education etc. But as we are working with selective samples, e.g. due to volunteer bias, our samples are usually more educated, healthier, older, more urban…

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## [How to decide if my phenotype is skewed and which transformation (log, sqrt, etc.) to use?](https://isgw-forum.colorado.edu/t/how-to-decide-if-my-phenotype-is-skewed-and-which-transformation-log-sqrt-etc-to-use/761)

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**Author:** [@jeongah.lee](https://isgw-forum.colorado.edu/u/jeongah.lee)\
**Replies:** 0\
**Last updated:** [June 2, 2026, 8:20pm UTC](https://isgw-forum.colorado.edu/t/how-to-decide-if-my-phenotype-is-skewed-and-which-transformation-log-sqrt-etc-to-use/761 "2026-06-02T20:20:33Z")

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How do you decide if a variable is “skewed enough” to need a transformation (e.g. any rule of thumb for skewness values or visual criteria)? For left‑ vs right‑skewed data, which simple transformations are usually r…

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## [Missing heritability vs non-transmitted allele](https://isgw-forum.colorado.edu/t/missing-heritability-vs-non-transmitted-allele/502)

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**Author:** [@anonymous15](https://isgw-forum.colorado.edu/u/anonymous15)\
**Replies:** 2\
**Last updated:** [April 5, 2026, 5:05pm UTC](https://isgw-forum.colorado.edu/t/missing-heritability-vs-non-transmitted-allele/502 "2026-04-05T17:05:39Z")

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Hi! sorry if this is basic but what is the difference or relation between missing heritability and non-transmitted alleles? Is it that the non-transmitted alleles contribute to missing heritability or are they completely…

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## [Statistics Primer (in more detail)](https://isgw-forum.colorado.edu/t/statistics-primer-in-more-detail/711)

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**Author:** [@lakshs31](https://isgw-forum.colorado.edu/u/lakshs31)\
**Replies:** 4\
**Last updated:** [March 4, 2025, 4:20pm UTC](https://isgw-forum.colorado.edu/t/statistics-primer-in-more-detail/711 "2025-03-04T16:20:31Z")

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Thank you for the statistical introduction this morning! My background is in bioinformatics and clinical medicine. One of my goals for the workshop is to identify more resources to help “shore up” my understanding of t…

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## [Signal and noise PCs](https://isgw-forum.colorado.edu/t/signal-and-noise-pcs/716)

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**Author:** [@Duncan](https://isgw-forum.colorado.edu/u/Duncan)\
**Replies:** 0\
**Last updated:** [March 3, 2025, 11:10pm UTC](https://isgw-forum.colorado.edu/t/signal-and-noise-pcs/716 "2025-03-03T23:10:03Z")

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Here’s a really nice talk detailing weird things that happen in high dimensions and signal/noise PCs:

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## [Paper on interpreting what PCA means](https://isgw-forum.colorado.edu/t/paper-on-interpreting-what-pca-means/715)

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**Author:** [@bneale](https://isgw-forum.colorado.edu/u/bneale)\
**Replies:** 0\
**Last updated:** [March 3, 2025, 11:09pm UTC](https://isgw-forum.colorado.edu/t/paper-on-interpreting-what-pca-means/715 "2025-03-03T23:09:50Z")

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Here’s the paper that Gil McVean on the interpretation of PCA: A Genealogical Interpretation of Principal Components Analysis

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## [Account for sample overlap using LDSC for PRS analysis](https://isgw-forum.colorado.edu/t/account-for-sample-overlap-using-ldsc-for-prs-analysis/713)

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**Author:** [@Wei\_Zhou](https://isgw-forum.colorado.edu/u/Wei_Zhou)\
**Replies:** 0\
**Last updated:** [March 3, 2025, 6:50pm UTC](https://isgw-forum.colorado.edu/t/account-for-sample-overlap-using-ldsc-for-prs-analysis/713 "2025-03-03T18:50:48Z")

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Here is a tool called EraSOR to account for the sample overlap problem using LDSC for PRS analysis https://academic.oup.com/gigascience/article/doi/10.1093/gigascience/giad043/7199403

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## [Generalizing HWE tests to account for structure](https://isgw-forum.colorado.edu/t/generalizing-hwe-tests-to-account-for-structure/712)

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**Author:** [@bneale](https://isgw-forum.colorado.edu/u/bneale)\
**Replies:** 0\
**Last updated:** [March 3, 2025, 6:35pm UTC](https://isgw-forum.colorado.edu/t/generalizing-hwe-tests-to-account-for-structure/712 "2025-03-03T18:35:35Z")

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Here’s a paper Extending Tests of Hardy–Weinberg Equilibrium to Structured Populations - PMC which enables a generalization for HWE to allow for structure.

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## [HE vs REML estimator in GWAS](https://isgw-forum.colorado.edu/t/he-vs-reml-estimator-in-gwas/648)

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**Author:** [@Ralph\_Porneso](https://isgw-forum.colorado.edu/u/Ralph_Porneso)\
**Replies:** 1\
**Last updated:** [May 20, 2024, 12:07am UTC](https://isgw-forum.colorado.edu/t/he-vs-reml-estimator-in-gwas/648 "2024-05-20T00:07:13Z")

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Hi, Are there some good references or is there someone who knows the scale of the difference in computation between REML and HE to estimate the variance components in a mixed effects model, say in GCTA fastGWA? I have …

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## [Relatedness and GRM](https://isgw-forum.colorado.edu/t/relatedness-and-grm/646)

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**Author:** [@soumej53](https://isgw-forum.colorado.edu/u/soumej53)\
**Replies:** 0\
**Last updated:** [April 29, 2024, 7:13am UTC](https://isgw-forum.colorado.edu/t/relatedness-and-grm/646 "2024-04-29T07:13:11Z")

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Hello, I wanted to ask if including grm in mixed model GWAS would be sufficient enough to adjust related individuals (first, second, third degree individuals) or is one recommended to remove the obviously related indivi…

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## [Ethics Issues](https://isgw-forum.colorado.edu/t/ethics-issues/643)

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**Author:** [@anonymous6](https://isgw-forum.colorado.edu/u/anonymous6)\
**Replies:** 0\
**Last updated:** [April 16, 2024, 12:03pm UTC](https://isgw-forum.colorado.edu/t/ethics-issues/643 "2024-04-16T12:03:22Z")

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Professor Keller shared some ethical problems to be discussed by the participants during the workshop. I found myself thinking about one of those issues. Would appreciate it if Professor Keller would list them out here a…

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## [GRM and population structure](https://isgw-forum.colorado.edu/t/grm-and-population-structure/641)

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**Author:** [@alicia\_schowe](https://isgw-forum.colorado.edu/u/alicia_schowe)\
**Replies:** 1\
**Last updated:** [April 3, 2024, 5:46am UTC](https://isgw-forum.colorado.edu/t/grm-and-population-structure/641 "2024-04-03T05:46:48Z")

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If we include a genetic relatedness matrix in our analyses (e.g., using linear mixed regression), is it still necessary to control for population structure using principal components in addition? Or does the GRM itself a…

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## [Unix session](https://isgw-forum.colorado.edu/t/unix-session/610)

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**Author:** [@luciana.vargas](https://isgw-forum.colorado.edu/u/luciana.vargas)\
**Replies:** 0\
**Last updated:** [March 4, 2024, 3:43pm UTC](https://isgw-forum.colorado.edu/t/unix-session/610 "2024-03-04T15:43:33Z")

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Here’s the link for the Unix/bash practical: https://qualtrics.ucl.ac.uk/jfe/form/SV\_0pHnuiW6juZ9ezs

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## [About QC of data from different microarrays](https://isgw-forum.colorado.edu/t/about-qc-of-data-from-different-microarrays/504)

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**Author:** [@Bruna](https://isgw-forum.colorado.edu/u/Bruna)\
**Replies:** 1\
**Last updated:** [March 7, 2023, 9:54pm UTC](https://isgw-forum.colorado.edu/t/about-qc-of-data-from-different-microarrays/504 "2023-03-07T21:54:51Z")

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Is that ok to merge datasets from different microarrays (for example, using bmerge plink command) before imputation? What are additional QC steps to check the quality of the merged dataset (e.g. flip issues)? What if the…

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## [Controlling for population stratification through PCs and replicability](https://isgw-forum.colorado.edu/t/controlling-for-population-stratification-through-pcs-and-replicability/505)

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**Author:** [@Giulio](https://isgw-forum.colorado.edu/u/Giulio)\
**Replies:** 3\
**Last updated:** [March 7, 2023, 11:22pm UTC](https://isgw-forum.colorado.edu/t/controlling-for-population-stratification-through-pcs-and-replicability/505 "2023-03-07T23:22:05Z")

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I recently came across this paper on controlling for population stratification with principal components, which claims the practice is highly problematic for genetic studies due to the black-box nature of the technique (…

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## [Beginner question R](https://isgw-forum.colorado.edu/t/beginner-question-r/328)

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**Author:** [@anonymous9](https://isgw-forum.colorado.edu/u/anonymous9)\
**Replies:** 3\
**Last updated:** [June 10, 2022, 8:33pm UTC](https://isgw-forum.colorado.edu/t/beginner-question-r/328 "2022-06-10T20:33:35Z")

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Hi, I have a really beginner R question. When i open R and run a project, i might be doing some analyses just for fun. But then I might want to focus on this course day 1. Is there a way of like doing different projects…
