From listmaster animalgenome.org Fri Feb 22 11:38:32 2019
Return-Path: <listmasteranimalgenome.org>
From: Patrik Waldmann <patrik.waldmannslu.se>
Postmaster: submission approved by list moderator
To: Members of AnGenMap <angenmapanimalgenome.org>
Subject: SV: software for exact p-values for association
analysis on single
Date: Fri, 22 Feb 2019 11:38:32 -0600
Juan and Andres,
GBLUP is ridge regression with a fixed penalty parameter (the ratio of the
error variance to the marker variance). The repeated single SNP model with
the G-matrix as a random effect is equivalent to GBLUP (given that the
marker matrix is properly standardized). Both these models are neither
unbiased nor exact. I did suggest a repeated single marker model without G
matrix correction, an unbiased model.
Best regards,
Patrik
________________________________________
Frn: Steibel, Juan [steibeljmsu.edu]
Skickat: den 22 februari 2019 14:08
Till: Patrik Waldmann; Members of AnGenMap
mne: Re: software for exact p-values for association analysis on single
Dear Patrick
I agree that these p-values may not be exact in the classical statistical
sense of the word.
But these are basically single SNP regressions. Please refer to the references
contributed by Andres in an email sent yesterday to this list (including the
ones I listed plus to more important references).
Some posters are assuming that this is a ridge regression test and it is not.
It is in fact a computationally efficient way of performing one-snp-at-a-time
testing using statistics derived fro REML estimated of an animal-centric
GBLUP model.
Cheers
JP
________________________________
.From: Patrik Waldmann <patrik.waldmannslu.se>
.Sent: Thursday, February 21, 2019 2:08 PM
.To: Members of AnGenMap <angenmapanimalgenome.org>
.Subject: SV: software for exact p-values for association analysis on
single
Max,
you're right, these test aren't exact. GBLUP is a form of ridge regression,
and as such provides shrinked, biased estimates of the regression
coefficients, and the variance (and standard deviation) of the estimates
will always be smaller compared to OLS estimates. The p-values cannot be
used in any form of hypothesis testing. It would be better to perform
single SNP regressions, and do some form of multiple comparison correction,
for example the local false discovery rate proposed by Bradley Efron.
Best regards,
Patrik Waldmann SLU, Uppsala Sweden
________________________________________
Frn: Rothschild, Max F [AN S] [mfrothsciastate.edu]
Skickat: den 21 februari 2019 18:08
Till: Members of AnGenMap
mne: Re: software for exact p-values for association analysis on single
step gblup
Dear colleagues
I admit I maybe out of my depth but it is hard for me to understand how the
tests can be exact.
Please explain.
Best Max
________________________________
.From: Steibel, Juan <steibeljmsu.edu>
.Sent: Wednesday, February 20, 2019 8:14:10 PM
.To: Members of AnGenMap <angenmapanimalgenome.org>
.Subject: Re: software for exact p-values for association analysis on
single step gblup
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/...n_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 (Araatuba/SP)
International Atomic Energy Agency (IAEA) Collaborating Centre on Animal
Genomics and Bioinformatics
Laboratory of Animal Biochemistry and Molecular Biology
|
