Error: rg out of bounds

[ghost]

Hi,

I'm using ldsc with two populations with the same phenotype. The qc and heritability steps are done correctly. However, when I run genetic correlation, the software doesn't calculate it. Here is the example:

Heritability of phenotype 1

Total Observed scale h2: 0.2318 (0.0145)
Lambda GC: 1.2464
Mean Chi^2: 1.2902
Intercept: 1.0276 (0.01)
Ratio: 0.0953 (0.0346)

Heritability of phenotype 2/2

Total Observed scale h2: 0.1568 (0.0258)
Lambda GC: 1.071
Mean Chi^2: 1.079
Intercept: 1.0114 (0.0077)
Ratio: 0.1445 (0.0981)

Genetic Covariance

Total Observed scale gencov: 0.2374 (0.0144)
Mean z1*z2: 0.5315
Intercept: 0.3695 (0.0061)

Genetic Correlation

Genetic Correlation: nan (nan) (rg out of bounds)
Z-score: nan (nan) (rg out of bounds)
P: nan (nan) (rg out of bounds)
WARNING: rg was out of bounds.
This often means that h2 is not significantly different from zero.

Summary of Genetic Correlation Results
p1 p2 rg se z p h2_obs h2_obs_se h2_int h2_int_se gcov_int gcov_int_se
da.sumstats.gz temp8.sumstats.gz 1.2452 0.0763 16.3274 6.2984e-60 0.1568 0.0258 1.0114 0.0077 0.3695 0.0061

I have tried the two files separately with other files (with different phenotype) and the program does calculate the genetic correlation. Thus, the files seem to be correct as qc and heritability can be calculated and also the genetic correlation with another file but not between these two files.

Could you help me?

Many thanks in advance!!!

Paula

[rkwalters]

Hi Paula, It looks like ldsc is successfully computing the rg (it lists rg=1.2452 in the results table at the bottom), but it get’s omitted from the main log because, as the error message indicates, that value is impossible. As a rule, ldsc prints this message when rg > 1.2. From the intercept for the genetic covariance it looks like you have a fair amount of sample overlap between these studies. Anecdotally, when true rg is high and there’s lots of sample overlap ldsc may tend to give these exaggerated estimates of rg >> 1. Cheers, Raymond

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On Mar 30, 2017, at 3:54 AM, PaulaRL37 ***@***.***> wrote: Hi, I'm using ldsc with two populations with the same phenotype. The qc and heritability steps are done correctly. However, when I run genetic correlation, the software doesn't calculate it. Here is the example: Heritability of phenotype 1 Total Observed scale h2: 0.2318 (0.0145) Lambda GC: 1.2464 Mean Chi^2: 1.2902 Intercept: 1.0276 (0.01) Ratio: 0.0953 (0.0346) Heritability of phenotype 2/2 Total Observed scale h2: 0.1568 (0.0258) Lambda GC: 1.071 Mean Chi^2: 1.079 Intercept: 1.0114 (0.0077) Ratio: 0.1445 (0.0981) Genetic Covariance Total Observed scale gencov: 0.2374 (0.0144) Mean z1*z2: 0.5315 Intercept: 0.3695 (0.0061) Genetic Correlation Genetic Correlation: nan (nan) (rg out of bounds) Z-score: nan (nan) (rg out of bounds) P: nan (nan) (rg out of bounds) WARNING: rg was out of bounds. This often means that h2 is not significantly different from zero. Summary of Genetic Correlation Results p1 p2 rg se z p h2_obs h2_obs_se h2_int h2_int_se gcov_int gcov_int_se da.sumstats.gz temp8.sumstats.gz 1.2452 0.0763 16.3274 6.2984e-60 0.1568 0.0258 1.0114 0.0077 0.3695 0.0061 I have tried the two files separately with other files (with different phenotype) and the program does calculate the genetic correlation. Thus, the files seem to be correct as qc and heritability can be calculated and also the genetic correlation with another file but not between these two files. Could you help me? Many thanks in advance!!! Paula — You are receiving this because you are subscribed to this thread. Reply to this email directly, view it on GitHub <#78>, or mute the thread <https://github.com/notifications/unsubscribe-auth/AILEvffU7Nuk_Se2Qgoo8kfaYvQqRjsoks5rq1-YgaJpZM4Mt_ai>.

[ghost]

Hi Raymond,

Many thanks for your quick answer!!!
I tried to run ldsc with two files with the same population (only to ensure the programme was running well) and it worked, giving a rg estimate of 1 (as expected). In this example, the overlap between individuals was 100%. If there are repeated people between my other files (but the overlap is <100%), why rg is >1?

Thanks again!!!

Paula

[rkwalters]

Hi Paula, The LD score estimator of rg isn’t bounded. If the true rg is near 1, and the LDSC estimate is the true value plus or minus some estimation error, it’s possible that the estimate (true rg + error) will be greater than 1. Sample overlap just makes this estimate less stable (i.e. more likely to estimate rg > 1). Estimating rg with two copies of the same GWAS is an exception since it basically has to (correctly) estimate rg=1 by definition because of how ldsc’s estimator of rg works. Cheers, Raymond

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On Apr 4, 2017, at 4:15 AM, PaulaRL37 ***@***.***> wrote: Hi Raymond, Many thanks for your quick answer!!! I tried to run ldsc with two files with the same population (only to ensure the programme was running well) and it worked, giving a rg estimate of 1 (as expected). In this example, the overlap between individuals was 100%. If there are repeated people between my other files (but the overlap is <100%), why rg is >1? Thanks again!!! Paula — You are receiving this because you commented. Reply to this email directly, view it on GitHub <#78 (comment)>, or mute the thread <https://github.com/notifications/unsubscribe-auth/AILEvWAhNpgGfkuUjDq5LzFoPqEggq28ks5rsfwvgaJpZM4Mt_ai>.

[ghost]

Hi Raymond,

I've checked the populations and, as expected, there is some overlap between them. Thank you for explaining me how the estimate is calculated.

Thank you very much!!!

Kind regards,
Paula

[rkwalters]

Hi Paula,
Closing this thread as resolved. If you have any more issues, feel free to follow up here or via the google group.
Cheers,
Raymond