Issues with Genetic correlation

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filippo abbondanza

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Sep 16, 2019, 11:07:36 AM9/16/19

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Hi,

I'm running some genetic correlation test using LDSC with my traits of interest (two quantitative measures of handedness) and several psychiatric traits from PGC, namely Bipolarism, Schizophrenia and Tourette syndrome. Everything goes fine with BP and SCZ but when I try to compute the genetic correlation with one of my trait and Tourette syndrome I got the error log reported below. Same if I try to calculate rg between my two traits. Do you know which can be the issue?

Best,

Filippo

SNP-heritability of my traits:

Trait 1

*********************************************************************

* LD Score Regression (LDSC)

* Version 1.0.1

* Broad Institute of MIT and Harvard / MIT Department of Mathematics

* GNU General Public License v3

*********************************************************************

Call:

./ldsc.py \

--h2 gripQ_sex_corrected.sumstats.gz \

--ref-ld-chr eur_w_ld_chr/ \

--out gripQ_sex_corrected \

--w-ld-chr eur_w_ld_chr/

Beginning analysis at Wed Sep 4 14:01:07 2019

Reading summary statistics from gripQ_sex_corrected.sumstats.gz ...

Read summary statistics for 359485 SNPs.

Reading reference panel LD Score from eur_w_ld_chr/[1-22] ...

Read reference panel LD Scores for 1290028 SNPs.

Removing partitioned LD Scores with zero variance.

Reading regression weight LD Score from eur_w_ld_chr/[1-22] ...

Read regression weight LD Scores for 1290028 SNPs.

After merging with reference panel LD, 355178 SNPs remain.

After merging with regression SNP LD, 355178 SNPs remain.

Using two-step estimator with cutoff at 30.

Total Observed scale h2: 0.023 (0.122)

Lambda GC: 1.0105

Mean Chi^2: 1.0059

Intercept: 1.0032 (0.0105)

Ratio: 0.5356 (1.7794)

Analysis finished at Wed Sep 4 14:01:21 2019

Total time elapsed: 14.41s

Trait 2:

*********************************************************************

* LD Score Regression (LDSC)

* Version 1.0.1

* Broad Institute of MIT and Harvard / MIT Department of Mathematics

* GNU General Public License v3

*********************************************************************

Call:

./ldsc.py \

--h2 grip_dex_sex_age.sumstats.gz \

--ref-ld-chr eur_w_ld_chr/ \

--out grip_dex_sex_age \

--w-ld-chr eur_w_ld_chr/

Beginning analysis at Fri Sep 6 15:01:30 2019

Reading summary statistics from grip_dex_sex_age.sumstats.gz ...

Read summary statistics for 359485 SNPs.

Reading reference panel LD Score from eur_w_ld_chr/[1-22] ...

Read reference panel LD Scores for 1290028 SNPs.

Removing partitioned LD Scores with zero variance.

Reading regression weight LD Score from eur_w_ld_chr/[1-22] ...

Read regression weight LD Scores for 1290028 SNPs.

After merging with reference panel LD, 355178 SNPs remain.

After merging with regression SNP LD, 355178 SNPs remain.

Using two-step estimator with cutoff at 30.

Total Observed scale h2: 0.3682 (0.1265)

Lambda GC: 1.0527

Mean Chi^2: 1.0463

Intercept: 1.0028 (0.0105)

Ratio: 0.0595 (0.2276)

Analysis finished at Fri Sep 6 15:02:06 2019

Total time elapsed: 35.81s

Genetic Correlation between my traits. I get the same error using each of my triat and Tourette summary stats

*********************************************************************

* LD Score Regression (LDSC)

* Version 1.0.1

* Broad Institute of MIT and Harvard / MIT Department of Mathematics

* GNU General Public License v3

*********************************************************************

Call:

./ldsc.py \

--ref-ld-chr eur_w_ld_chr/ \

--out Genetic_correlation/grip_dex_sex_age_gripQ_sex_corrected \

--rg grip_dex_sex_age.sumstats.gz,gripQ_sex_corrected.sumstats.gz \

--w-ld-chr eur_w_ld_chr/

Beginning analysis at Mon Sep 16 16:02:33 2019

Reading summary statistics from grip_dex_sex_age.sumstats.gz ...

Read summary statistics for 359485 SNPs.

Reading reference panel LD Score from eur_w_ld_chr/[1-22] ...

Read reference panel LD Scores for 1290028 SNPs.

Removing partitioned LD Scores with zero variance.

Reading regression weight LD Score from eur_w_ld_chr/[1-22] ...

Read regression weight LD Scores for 1290028 SNPs.

After merging with reference panel LD, 355178 SNPs remain.

After merging with regression SNP LD, 355178 SNPs remain.

Computing rg for phenotype 2/2

Reading summary statistics from gripQ_sex_corrected.sumstats.gz ...

Read summary statistics for 1217311 SNPs.

After merging with summary statistics, 355178 SNPs remain.

355178 SNPs with valid alleles.

ERROR computing rg for phenotype 2/2, from file gripQ_sex_corrected.sumstats.gz.

Traceback (most recent call last):

File "/storage/home/users/fa36/LDSC/ldsc/ldscore/sumstats.py", line 410, in estimate_rg

rghat = _rg(loop, args, log, M_annot, ref_ld_cnames, w_ld_cname, i)

File "/storage/home/users/fa36/LDSC/ldsc/ldscore/sumstats.py", line 539, in _rg

intercept_gencov=intercepts[2], n_blocks=n_blocks, twostep=args.two_step)

File "/storage/home/users/fa36/LDSC/ldsc/ldscore/regressions.py", line 705, in __init__

np.multiply(hsq1.tot_delete_values, hsq2.tot_delete_values))

FloatingPointError: invalid value encountered in sqrt

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

grip_dex_sex_age.sumstats.gz gripQ_sex_corrected.sumstats.gz NA NA NA NA NA NA NA NA NA NA

Analysis finished at Mon Sep 16 16:03:03 2019

Total time elapsed: 30.29s

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