Arbel Harpak

@arbelharpak

Population genetics postdoc at Columbia University with .

Vrijeme pridruživanja: srpanj 2014.

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  1. Prikvačeni tweet
    7. svi 2019.

    In work by , we checked whether polygenic scores can be assumed to be portable *within* an ancestry group. They cannot. [[thread]]

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  2. 30. sij

    I think this is key for almost all applications of polygenic scores, and specifically for tackling the portability problem.

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  3. 30. sij

    One more lingering question: can the portability problem be mitigated by borrowing ideas from other fields, e.g. where the learning and prediction sets are known to differ in important ways? (<-- not a rhetorical question) h/t

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  4. 30. sij

    We developed a test to detect the substantial effect of either population structure confounding, assortative mating or indirect genetic effects. But there is still work ahead to *quantify* the contribution of direct genetic effects vs. other factors to polygenic scores.

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  5. 30. sij

    Thanks to a reviewer suggestion, we matched the “diverse” GWAS (eg a sample of an equal number of men and women) sample size to the non-diverse GWAS (eg only men or only women). This helps demonstrate that the performance/portability of diverse samples is not necessarily better.

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  6. 30. sij

    We hypothesize instead that there are large differences in genetic variance across strata. In other words, this is potential evidence for substantial GxE.

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  7. 30. sij

    We initially expected heritability differences to have little to do with genetic effects; and that they are mostly due to independent differences in environmental variance across strata. However, such a model does not fit the data.

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  8. 30. sij

    One analysis that we had not highlighted previously asks why SNP heritability estimates vary dramatically across (socio-economic status/sex/age) strata.

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  9. 30. sij
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  10. 30. sij

    An updated version of our ( and ) work on the factors affecting the performance of polygenic scores--beyond genetic ancestry—is accepted and now up [thread]

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  11. proslijedio/la je Tweet
    28. sij

    This is incorrect. Here's some recent lit on how & why existing PGS methods do not fully separate genetic from environmental effects on traits, particularly when comparing across populations.

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  12. proslijedio/la je Tweet
    27. sij

    The Leffler Lab is launching! We have opportunities for grad students and postdocs to work on human and macaque evolutionary genomics, malaria adaptation, structural variation, and more -- see for further info and get in touch!

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  13. 24. sij

    Piece today by on the income GWAS study ending with some (not far-fetched) speculations on the underlying motivation

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  14. 17. pro 2019.

    But for all other applications/interpretations, perhaps we would only gain from holding off until we have a better handle on this, e.g. a decomposition of GWAS associations into the various contributing factors?

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  15. 17. pro 2019.

    by no means should my thoughts stop anyone from CRISPRring 

    Tweet je nedostupan.
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  16. 17. pro 2019.

    *re the low h2: even this nonzero SNP heritability estimates are quite possibly aided by {stratification, mating patterns, indirect effects} in the same way that prediction accuracy is aided by them

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  17. 17. pro 2019.

    But to me, this combination just emphasizes the near-impossibility of saying anything meaningful about causality with GWAS data here.  Downstream analysis, importantly MR, are not at all immune

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  18. 17. pro 2019.

    To be fair, the magnitude of the evidence here is due to a combination of (1) the presence of these factors and (2) the low* SNP heritability of household income.

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  19. 17. pro 2019.

    In our test for the substantial effect of {population stratification, assortative mating and indirect genetic effects} on UKB GWAS associations, household income almost won the most-clearly-problematic pageant

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  20. proslijedio/la je Tweet
    6. pro 2019.

    (Thread) New preprint out. Population genetics of the coral Acropora millepora: Towards a genomic predictor of bleaching. We are very excited about this work, here a few of the highlights (1/n)

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  21. proslijedio/la je Tweet
    21. stu 2019.

    New paper in ! We provide an empirical and theoretical evaluation of the expected outcomes of selecting human IVF embryos for traits such as height or IQ. 1/10 With , Or Zuk, , and others.

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