### Mendelian randomisation ----
library(TwoSampleMR)
## TwoSampleMR version 0.5.6
## [>] New: Option to use non-European LD reference panels for clumping etc
## [>] Some studies temporarily quarantined to verify effect allele
## [>] See news(package='TwoSampleMR') and https://gwas.mrcieu.ac.uk for further details
ao <- available_outcomes()
## API: public: http://gwas-api.mrcieu.ac.uk/
exposure_dat.insomnia <- extract_instruments(c('ukb-a-13','ukb-b-3957'))
## Server code: 502; Server is possibly experiencing traffic, trying again...
## Server code: 502; Server is possibly experiencing traffic, trying again...
## Server code: 502; Server is possibly experiencing traffic, trying again...
## Retry succeeded!
exposure_dat.insomnia <- clump_data(exposure_dat.insomnia)
## Please look at vignettes for options on running this locally if you need to run many instances of this command.
## Clumping ukb-a-13, 30 variants, using EUR population reference
## Removing 1 of 30 variants due to LD with other variants or absence from LD reference panel
## Clumping ukb-b-3957, 42 variants, using EUR population reference
outcome_dat.apnoea <- extract_outcome_data(exposure_dat.insomnia$SNP,
c('ukb-b-16781','ukb-d-G6_SLEEPAPNO'),
proxies = 1, rsq = 0.8, align_alleles = 1, palindromes = 1, maf_threshold = 0.3)
## Extracting data for 62 SNP(s) from 2 GWAS(s)
## Finding proxies for 6 SNPs in outcome ukb-b-16781
## Extracting data for 6 SNP(s) from 1 GWAS(s)
dat.insomnia_on_apnoea <- harmonise_data(exposure_dat.insomnia, outcome_dat.apnoea, action = 2)
## Harmonising Sleeplessness / insomnia || id:ukb-a-13 (ukb-a-13) and Diagnoses - main ICD10: G47.3 Sleep apnoea || id:ukb-b-16781 (ukb-b-16781)
## Removing the following SNPs for being palindromic with intermediate allele frequencies:
## rs10280045, rs2644128
## Harmonising Sleeplessness / insomnia || id:ukb-b-3957 (ukb-b-3957) and Diagnoses - main ICD10: G47.3 Sleep apnoea || id:ukb-b-16781 (ukb-b-16781)
## Removing the following SNPs for being palindromic with intermediate allele frequencies:
## rs2644128, rs2803296, rs8180817
## Harmonising Sleeplessness / insomnia || id:ukb-b-3957 (ukb-b-3957) and Sleep apnoea || id:ukb-d-G6_SLEEPAPNO (ukb-d-G6_SLEEPAPNO)
## Removing the following SNPs for being palindromic with intermediate allele frequencies:
## rs2644128, rs2803296, rs8180817
## Harmonising Sleeplessness / insomnia || id:ukb-a-13 (ukb-a-13) and Sleep apnoea || id:ukb-d-G6_SLEEPAPNO (ukb-d-G6_SLEEPAPNO)
## Removing the following SNPs for being palindromic with intermediate allele frequencies:
## rs10280045, rs2644128
mr_results.insomnia_on_apnoea <- mr(dat.insomnia_on_apnoea)
## Analysing 'ukb-a-13' on 'ukb-b-16781'
## Analysing 'ukb-a-13' on 'ukb-d-G6_SLEEPAPNO'
## Analysing 'ukb-b-3957' on 'ukb-b-16781'
## Analysing 'ukb-b-3957' on 'ukb-d-G6_SLEEPAPNO'
mr_results.insomnia_on_apnoea.sig = subset(mr_results.insomnia_on_apnoea, pval < 0.05)
exposure_dat.apnoea <- extract_instruments(c('ukb-b-16781','ukb-d-G6_SLEEPAPNO','finn-b-G6_SLEEPAPNO_INCLAVO','finn-b-G6_SLEEPAPNO'))
outcome_dat.insomnia <- extract_outcome_data(exposure_dat.apnoea$SNP, c('ukb-b-3957','ukb-a-13','ebi-a-GCST004695','ebi-a-GCST006487','ebi-a-GCST006488'), proxies = 1, rsq = 0.8, align_alleles = 1, palindromes = 1, maf_threshold = 0.3)
## Extracting data for 5 SNP(s) from 5 GWAS(s)
## Finding proxies for 1 SNPs in outcome ebi-a-GCST004695
## Extracting data for 1 SNP(s) from 1 GWAS(s)
## Finding proxies for 1 SNPs in outcome ebi-a-GCST006487
## Extracting data for 1 SNP(s) from 1 GWAS(s)
## Finding proxies for 1 SNPs in outcome ebi-a-GCST006488
## Extracting data for 1 SNP(s) from 1 GWAS(s)
dat.apnoea_on_insomnia <- harmonise_data(exposure_dat.apnoea, outcome_dat.insomnia, action = 2)
## Harmonising Sleep apnoea, including avohilmo || id:finn-b-G6_SLEEPAPNO_INCLAVO (finn-b-G6_SLEEPAPNO_INCLAVO) and Insomnia complaints || id:ebi-a-GCST004695 (ebi-a-GCST004695)
## Harmonising Sleep apnoea || id:finn-b-G6_SLEEPAPNO (finn-b-G6_SLEEPAPNO) and Insomnia complaints || id:ebi-a-GCST004695 (ebi-a-GCST004695)
## Harmonising Sleep apnoea, including avohilmo || id:finn-b-G6_SLEEPAPNO_INCLAVO (finn-b-G6_SLEEPAPNO_INCLAVO) and Insomnia complaints || id:ebi-a-GCST006487 (ebi-a-GCST006487)
## Harmonising Sleep apnoea || id:finn-b-G6_SLEEPAPNO (finn-b-G6_SLEEPAPNO) and Insomnia complaints || id:ebi-a-GCST006487 (ebi-a-GCST006487)
## Harmonising Sleep apnoea, including avohilmo || id:finn-b-G6_SLEEPAPNO_INCLAVO (finn-b-G6_SLEEPAPNO_INCLAVO) and Insomnia complaints || id:ebi-a-GCST006488 (ebi-a-GCST006488)
## Harmonising Sleep apnoea || id:finn-b-G6_SLEEPAPNO (finn-b-G6_SLEEPAPNO) and Insomnia complaints || id:ebi-a-GCST006488 (ebi-a-GCST006488)
## Harmonising Sleep apnoea || id:finn-b-G6_SLEEPAPNO (finn-b-G6_SLEEPAPNO) and Sleeplessness / insomnia || id:ukb-a-13 (ukb-a-13)
## Harmonising Sleep apnoea, including avohilmo || id:finn-b-G6_SLEEPAPNO_INCLAVO (finn-b-G6_SLEEPAPNO_INCLAVO) and Sleeplessness / insomnia || id:ukb-a-13 (ukb-a-13)
## Harmonising Sleep apnoea, including avohilmo || id:finn-b-G6_SLEEPAPNO_INCLAVO (finn-b-G6_SLEEPAPNO_INCLAVO) and Sleeplessness / insomnia || id:ukb-b-3957 (ukb-b-3957)
## Harmonising Sleep apnoea || id:finn-b-G6_SLEEPAPNO (finn-b-G6_SLEEPAPNO) and Sleeplessness / insomnia || id:ukb-b-3957 (ukb-b-3957)
mr_results.apnoea_on_insomnia <- mr(dat.apnoea_on_insomnia)
## Analysing 'finn-b-G6_SLEEPAPNO' on 'ebi-a-GCST004695'
## Analysing 'finn-b-G6_SLEEPAPNO' on 'ebi-a-GCST006487'
## Analysing 'finn-b-G6_SLEEPAPNO' on 'ebi-a-GCST006488'
## Analysing 'finn-b-G6_SLEEPAPNO' on 'ukb-a-13'
## Analysing 'finn-b-G6_SLEEPAPNO' on 'ukb-b-3957'
## Analysing 'finn-b-G6_SLEEPAPNO_INCLAVO' on 'ebi-a-GCST004695'
## Analysing 'finn-b-G6_SLEEPAPNO_INCLAVO' on 'ebi-a-GCST006487'
## Analysing 'finn-b-G6_SLEEPAPNO_INCLAVO' on 'ebi-a-GCST006488'
## Analysing 'finn-b-G6_SLEEPAPNO_INCLAVO' on 'ukb-a-13'
## Analysing 'finn-b-G6_SLEEPAPNO_INCLAVO' on 'ukb-b-3957'
mr_results.apnoea_on_insomnia.sig = subset(mr_results.apnoea_on_insomnia, pval < 0.1)
mr_results.apnoea_on_insomnia.sig
## id.exposure id.outcome
## 17 finn-b-G6_SLEEPAPNO ukb-a-13
## 42 finn-b-G6_SLEEPAPNO_INCLAVO ukb-a-13
## outcome
## 17 Sleeplessness / insomnia || id:ukb-a-13
## 42 Sleeplessness / insomnia || id:ukb-a-13
## exposure
## 17 Sleep apnoea || id:finn-b-G6_SLEEPAPNO
## 42 Sleep apnoea, including avohilmo || id:finn-b-G6_SLEEPAPNO_INCLAVO
## method nsnp b se pval
## 17 Weighted median 5 0.02724078 0.01461098 0.06226480
## 42 Weighted median 5 0.02755070 0.01409077 0.05055587