dariushghasemi / kidneyInCHRIS

Genetic determinants of Kidney function in the CHRIS study
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KidneyInCHRIS part of TrainCKDis Horizon 2020 EU Project

Genetic determinants of Kidney function in The Corporative Health Research In South Tyrol (CHRIS) study

Several issues have been created to track the progress in the project. Here is the list of the issues in chronological order:

1. Picking the discovery Loci

2. Subtracting CHRIS from CKDGen

3. Phenotype creation

4. Conducting GWAS on renal function

5. Comparing replicated variants effect magnitude with discovery studies

6. Comparing the 147 CKDGen Loci in CHRIS

7. Excluding batch effects from the health traits using transformation

8. Extracting dosage from VCF


## 9. Phenome-wide mediation analysis

## 10. Kidney interaction with Thyroid
- This analysis have been throughly explained earlier in this [repository](https://github.com/DariushG3/SNP-TSHcat_Interaction_Model)
- As we observed the significants interaction for two SNPs out of 3 in one replicated locus, we tried to elucidate this findings. By centralizing TSH (0-mean-centered) we realized adjustment in SNP regression coefficients but still interaction effects and the corresponding P-values remained stable.
- Another important thing we found was that the significant interaction only occurs when we exclude the cases with cancers/renal carcinoma/alternation of thyroid function due to pregnancy which were ~9,700 individuals. If we apply the previous model on the entire CHRIS 10K consisting of ~10,140 individuals the significance of interaction terms goes away and there would not be any significant interaction antymore.
```R
# Regular TSH levels
lm(eGFRw.log.Res ~ SNP * TSH + Sex + Age + PC1 + PC2 + PC3 + PC4 + PC5 + PC6 + PC7 + PC8 + PC9 + PC10)

11. Sensitivity Analyses

Sensitivity of SNPs' dosage to having missing in FT3/4

Sensitivity test for missing in FT4:

wilcox.test(SNP ~ FT4_indicator, data = vcfReg)

### Sensitivity of the FT3/4-adjusted association of SNPs on log(eGFR) to Municipality
- Here we test how the association of SNPs on log(eGFR) changes when we adjust the LR model both for FT3/4 and municipality. This variable indicates the unmeasured differences in allele frequency of the SNPs between different villages in the region where CHRIS study was conducted. Truly, this idea is coming from where we thought adding municipality could affect the SNP-Kidney adjusted association FT3 or FT4, and in this way we might capture the batch effects in order to have an unbiased idea of the interaction between the kidney and thyroid traits.
- Thus, we tested the association of the SNP and kidney adjusted for FT3/4 once without adjusting for municipality and once with adjusting for it as below:
```R
#Sensitivity test for FT3:
log(eGFR) ~ SNP +FT3 + Sex + Age vs. log(eGFR) ~ SNP +FT3 + Sex + Age + Municipality

#Sensitivity test for FT4:
log(eGFR) ~ SNP +FT4 + Sex + Age vs. log(eGFR) ~ SNP +FT4 + Sex + Age + Municipality

12. Interrogating 163 replicated SNPs in Phenoscanner

13. Publication and manuscript revision

zgrep -E 'rs74748843|rs807624$|rs28817415|rs10062079|rs3812036|rs57514204|rs819196|rs2039424|rs7113042|rs59646751|rs77924615' $CKDGen_TA > $OUTPUT



- I got sick, probably covid-19 infection and couldn't work on the shroom3 draft paper. (Sat, 20:55, 09-Dec-23) 

- Just recovered and after submitting paper revision tomorrow noon, I will work on the 2nd paper to finish the discussion (Sun, 23:22, 10-Dec-23).

- Fig. 3A was modified and Fig.3 was changed accordingly(Mon, 16:30, 11-Dec-23).

- We submitted the revised manuscript to the journal (Mon, 23:59, 11-Dec-23).

Dariush