From listmaster animalgenome.org Tlistmaster Feb 21 13:55:59 2019
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From: "Steibel, Juan" <steibeljmsu.edu>
Subject: Re: software for exact p-values for association
analysis on single step gblup
Postmaster: submission approved by list moderator
To: Members of AnGenMap <angenmapanimalgenome.org>
Date: Thu, 21 Feb 2019 13:55:59 -0600
Dear Yuri,
The proof in the cited appendix is for the case where there is no iteration
to re-weight markers.
Iterating to differential weight markers seems like a good idea to me, but
I have no experience implementing it. However, Andrés, Ignacio and Ignacy
have extensive experience on that and they may be able to share their
experience.
Personally, I think It's great to have this implemented in BLUPF90, with the
possibility of (optinallt) re-weighting marker effects after the REML fit,
to produce a formal hypothesis test of association for large datasets
including genotyped and non-genotyped animals.
Cheers
JP
________________________________
.From: Yuri Tani Utsunomiya <ytutsunomiyagmail.com>
.Sent: Thursday, February 21, 2019 8:09 AM
.To: Steibel, Juan
.Cc: Members of AnGenMap
.Subject: Re: software for exact p-values for association analysis on single
step gblup
Thanks Juan!
Much clearer now with Appendix S1 from
https://www.ncbi.nlm.nih.gov/...articles/PMC4738412/
The description in MS ID#: BIORXIV/2019/555243 was a little bit confusing
to me (and also to Daniel as I see).
Do you know if equivalence of t-values between GBLUP and EMMAX break after
iterating on marker weights?
Cheers
On Wed, Feb 20, 2019 at 11:14 PM Steibel, Juan <steibeljmsu.edu> wrote:
Dear Yuri
It is in fact a fixed SNP effect test derived from an animal centric GBLUP.
I recommend you take a look on the following paper (especially the
appendix): https://onlinelibrary.wiley.com/...oi/10.1111/age.12378
https://www.ncbi.nlm.nih.gov/pubmed/26607299
Meta-analysis of genome-wide association from genomic prediction models. -
PubMed - NCBI https://www.ncbi.nlm.nih.gov/pubmed/26607299 Anim Genet. 2016
Feb;47(1):36-48. doi: 10.1111/age.12378. Epub 2015 Nov 26. Meta-Analysis;
Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
http://www.ncbi.nlm.nih.gov
Where we show analytically the equivalence between a "snp-test" in a GBLUP
model and the EMMAX approach used for GWA (which is the answer to your
question, I guess).
Also, here are some simulation results showing the properties of the test
when we first proposed it: https://www.ncbi.nlm.nih.gov/pubmed/25038782
Rapid screening for phenotype-genotype associations by linear transformations
of genomic evaluations - PubMed - NCBI BMC Bioinformatics. 2014 Jul 19;15:246.
doi: 10.1186/1471-2105-15-246. Research Support, Non-U.S. Gov't; Research
Support, U.S. Gov't, Non-P.H.S. http://www.ncbi.nlm.nih.gov
These two paper (and others) are cited in Andres' manuscript as the basis for
their implementation in BLUPF90.
Cheers
JP
________________________________
.From: Yuri Tani Utsunomiya <ytutsunomiyagmail.com>
.Sent: Wednesday, February 20, 2019 9:43 AM
.To: Members of AnGenMap <angenmapanimalgenome.org>
.Subject: Re: software for exact p-values for association analysis on single
step gblup
Dear Andres,
I am a little bit confused with the proposed test.
As far as my limited knowledge goes, classic t-distributed statistics are
ratios between estimates of parameters of interest and their respective
standard errors. In the manuscript, the denominator of the ratio seems to
be the square root of the variance due to the tested marker instead (i.e.,
marker standard deviation), which is not the same as the standard error of
the estimate. The latest information I had was that the standard errors of
marker effects in GBLUP and ssGBLUP do not have a simple or even known
expression for fast computation, and therefore they should be approximated
with resampling procedures such as bootstraping, subsampling or
jackknifing. Please do not take this observation as a critic, but rather as
a question that - I believe - many of us users of blupf90 have. Last but
not least, I apologize if my read of the proposal is incorrect.
Cheers,
Yuri Utsunomiya
On Wed, Feb 20, 2019 at 10:36 AM Andres Legarra-Albizu <andres.legarrainra.fr> wrote:
> Dear all,
>
> thanks to collaborative work and extensive programming, I, on behalf of all
> the blupf90 team, am happy to announce that the blupf90 suite now computes
> exact p-values for gwas analysis - same as “one at a time” classical
> gwas by regression. The authoritative reference is this biorxiv deposit:
>
> MS ID#: BIORXIV/2019/555243
>
> MS TITLE: Exact p-values for large-scale single step genome-wide
> association, with an application for birth weight in American Angus
>
> These requires the use of OPTION snp_p_value in programs blupf90 (or
> blupf90test) and postGSf90. More details in the corresponding sections in
> the wiki:
>
> http://nce.ads.uga.edu/...application_programs
>
> regards, Andres
>
> --
> Andres Legarra
> +33 561285182
> INRA, UMR1388 GenPhySE
> CS 52627
> 31326 Castanet Tolosan, France
--
*Yuri T. Utsunomiya*
DVM/MSc/PhD
Sao Paulo State University (UNESP - Brazil)
School of Veterinary Medicine - Department of Support, Production and
Animal Health (Araçatuba/SP)
International Atomic Energy Agency (IAEA) Collaborating Centre on Animal
Genomics and Bioinformatics
Laboratory of Animal Biochemistry and Molecular Biology
--
Yuri T. Utsunomiya
DVM/MSc/PhD
Sao Paulo State University (UNESP - Brazil)
School of Veterinary Medicine - Department of Support, Production and Animal
Health (Araçatuba/SP)
International Atomic Energy Agency (IAEA) Collaborating Centre on Animal
Genomics and Bioinformatics
Laboratory of Animal Biochemistry and Molecular Biology
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