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Mendelian randomisation?
Mendelian randomisation is interesting, but why is it mentioned as something that PRS can be used for? I mean sure, you can use "many SNPs as instruments" which is kinda like PRS - but still PRS is not really in itself a MR tool is it? Yinwang888 (talk) 01:18, 8 February 2020 (UTC)
30th October, 2016. Page created
I wrote this page today because it seemed important to have and was missing. I have filled in a broad selection of literature, but from human studies and from animal studies. There are many things that could be improved:
- Adding more example papers. In particular, there are more relevant papers about various SES measures that show that these can be predicted from polygenic scores, in line with the non-zero heritability of such traits. Likewise, there are related findings for cognitive ability.
- There are other uses of polygenic scores rather than prediction/breeding: Examining the genetic architecture of traits, in particular the degree of polygenicity, estimating genetic correlations directly by correlating the weights vectors, examining genetic causes of group differences, and detecting (natural) selection.
- One could add more about the methods used. For many of the standard methods, there exist Bayesian equivalents which also tend to fare well in comparisons.
- Discussion of how the polygenic prediction relates to heritability. The heritability sets the upper limit of what is possible using polygenic scores. Since heritabilities are in units of variance, one should take the square root. Note that due to the ^2 transformation, 50% of the maximum predictive validity is attained already when one can only account for 25% of the genetic variance. One can also discuss the nature of the polygenic score construction, e.g. additivity vs. non-additive and nonlinear models.
--Deleet (talk) 21:01, 30 October 2016 (UTC)
Unclear sentence
The discussed sentence appears to have been removed or edited at this point --Stal potaten (talk) 22:52, 13 April 2021 (UTC)
In a genome-wide association study (GWAS), polygenic scores having substantially higher predictive performance than the genome-wide statistically-significant hits indicates that the trait in question is affected by a larger number of variants than just the hits and larger sample sizes will yield more hits; a conjunction of low variance explained and high heritability as measured by genome-wide complex trait analysis (GCTA), twin studies or other methods, indicates that a trait may be massively polygenic and affected by thousands of variants.
To start with: "hit indicates" or "hits indicate", but the problem clearly runs deeper than that. — MaxEnt 01:00, 7 May 2020 (UTC)
- Edited the above quote to reflect my last quick edit (properly glossing GCTA). The text above dates almost all the way back to article inception. Flagged that sentence as unclear and the article as confusing. But this is not my kettle of fish, so that's a drive-by. Feel free to revert those flags if annoyed. — MaxEnt 01:09, 7 May 2020 (UTC)
- I was wrong. There is a correct parse, it's just not a happy one. "having hits indicates that the trait in question is affected by a larger number of variants than just the hits ... and larger sample sizes will yield more hits". You can't cue up a massive "having" clause in that way outside of an academic journal, as it's tremendously subjunctive and the common reader has no bearings yet. — MaxEnt 01:16, 7 May 2020 (UTC)
- Well, I took another run at this having finally made my way through parsing the above, and not much joy. While I don't have a graduate degree in this field, I'm not an unsophisticated reader in this subject area. It really should not be this difficult. Additionally flagged for expert-subject genetics. — MaxEnt 01:30, 7 May 2020 (UTC)
- I'd be inclined to agree that that sentence is very hard to parse, but also that it's perhaps not even appropriate to appear so early in the introductory text of the article. The point it's making is important to a technical understanding of polygenic scores, but does not relate directly to explaining what the score means, where it comes from, and other obvious lede-relevant facts, and so the point itself may not belong in the lede at all. I'll see if I can revise it a bit.
- I'm not responsible for that bit of unparsable jargon but I have contributed a fair amount to the rest of the article, so please feel free to point out any other concepts or phrasings that might be difficult for nonprofessionals. -Ferahgo the Assassin (talk) 19:50, 7 May 2020 (UTC)
Larger page edit, April 2021
I have in a series of edits added a few sections and (in my eyes) improved many of the already existing ones. The page may still not give an entirely coherent read but is more comprehensive, somewhat easier to read and contains more updated results. Although not perfect, I think the page does no longer merit the flags.
Unless a discussion here starts within a week, I intend to resolve the old flags. --Stal potaten (talk) 22:59, 13 April 2021 (UTC)
- Sounds good to me. I'm happy to try and tackle any sections that are still considered less than coherent, too. -Ferahgo the Assassin (talk) 23:38, 23 April 2021 (UTC)