Investigating skin-related measures in relation to number of children fathered

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

Childhood sunburn occasions

d <- make_dat("ukb-b-13246", "ukb-b-2227")
## API: public: http://gwas-api.mrcieu.ac.uk/
## Extracting data for 81 SNP(s) from 1 GWAS(s)
## Harmonising Childhood sunburn occasions || id:ukb-b-13246 (ukb-b-13246) and Number of children fathered || id:ukb-b-2227 (ukb-b-2227)
## Removing the following SNPs for incompatible alleles:
## rs111650620
d_mr<-mr(d)
## Analysing 'ukb-b-13246' on 'ukb-b-2227'
d_mr
##   id.exposure id.outcome                                      outcome
## 1 ukb-b-13246 ukb-b-2227 Number of children fathered || id:ukb-b-2227
## 2 ukb-b-13246 ukb-b-2227 Number of children fathered || id:ukb-b-2227
## 3 ukb-b-13246 ukb-b-2227 Number of children fathered || id:ukb-b-2227
## 4 ukb-b-13246 ukb-b-2227 Number of children fathered || id:ukb-b-2227
## 5 ukb-b-13246 ukb-b-2227 Number of children fathered || id:ukb-b-2227
##                                        exposure                    method nsnp
## 1 Childhood sunburn occasions || id:ukb-b-13246                  MR Egger   81
## 2 Childhood sunburn occasions || id:ukb-b-13246           Weighted median   81
## 3 Childhood sunburn occasions || id:ukb-b-13246 Inverse variance weighted   81
## 4 Childhood sunburn occasions || id:ukb-b-13246               Simple mode   81
## 5 Childhood sunburn occasions || id:ukb-b-13246             Weighted mode   81
##             b         se         pval
## 1 -0.05901597 0.01741398 1.096818e-03
## 2 -0.05937328 0.01542528 1.185582e-04
## 3 -0.04659383 0.01318919 4.112956e-04
## 4 -0.02174409 0.03437179 5.287896e-01
## 5 -0.05602069 0.01123614 3.511720e-06
mr_scatter_plot(d_mr,d)
## $`ukb-b-13246.ukb-b-2227`

## 
## attr(,"split_type")
## [1] "data.frame"
## attr(,"split_labels")
##   id.exposure id.outcome
## 1 ukb-b-13246 ukb-b-2227
d <- make_dat("ukb-b-2227", "ukb-b-13246")
## Extracting data for 3 SNP(s) from 1 GWAS(s)
## Harmonising Number of children fathered || id:ukb-b-2227 (ukb-b-2227) and Childhood sunburn occasions || id:ukb-b-13246 (ukb-b-13246)
d_mr<-mr(d)
## Analysing 'ukb-b-2227' on 'ukb-b-13246'
d_mr
##   id.exposure  id.outcome                                       outcome
## 1  ukb-b-2227 ukb-b-13246 Childhood sunburn occasions || id:ukb-b-13246
## 2  ukb-b-2227 ukb-b-13246 Childhood sunburn occasions || id:ukb-b-13246
## 3  ukb-b-2227 ukb-b-13246 Childhood sunburn occasions || id:ukb-b-13246
## 4  ukb-b-2227 ukb-b-13246 Childhood sunburn occasions || id:ukb-b-13246
## 5  ukb-b-2227 ukb-b-13246 Childhood sunburn occasions || id:ukb-b-13246
##                                       exposure                    method nsnp
## 1 Number of children fathered || id:ukb-b-2227                  MR Egger    3
## 2 Number of children fathered || id:ukb-b-2227           Weighted median    3
## 3 Number of children fathered || id:ukb-b-2227 Inverse variance weighted    3
## 4 Number of children fathered || id:ukb-b-2227               Simple mode    3
## 5 Number of children fathered || id:ukb-b-2227             Weighted mode    3
##             b        se      pval
## 1  4.54375108 3.8056959 0.4438714
## 2  0.06624927 0.1128342 0.5571109
## 3  0.25647710 0.2311857 0.2672583
## 4 -0.02890785 0.1128213 0.8217227
## 5 -0.01370377 0.1141913 0.9154460
mr_scatter_plot(d_mr,d)
## $`ukb-b-2227.ukb-b-13246`

## 
## attr(,"split_type")
## [1] "data.frame"
## attr(,"split_labels")
##   id.exposure  id.outcome
## 1  ukb-b-2227 ukb-b-13246

Ease of skin tanning

d <- make_dat("ukb-b-533", "ukb-b-2227")
## Extracting data for 135 SNP(s) from 1 GWAS(s)
## Harmonising Ease of skin tanning || id:ukb-b-533 (ukb-b-533) and Number of children fathered || id:ukb-b-2227 (ukb-b-2227)
## Removing the following SNPs for incompatible alleles:
## rs111650620, rs2094756, rs7300019, rs9545154
d_mr<-mr(d)
## Analysing 'ukb-b-533' on 'ukb-b-2227'
d_mr
##   id.exposure id.outcome                                      outcome
## 1   ukb-b-533 ukb-b-2227 Number of children fathered || id:ukb-b-2227
## 2   ukb-b-533 ukb-b-2227 Number of children fathered || id:ukb-b-2227
## 3   ukb-b-533 ukb-b-2227 Number of children fathered || id:ukb-b-2227
## 4   ukb-b-533 ukb-b-2227 Number of children fathered || id:ukb-b-2227
## 5   ukb-b-533 ukb-b-2227 Number of children fathered || id:ukb-b-2227
##                               exposure                    method nsnp
## 1 Ease of skin tanning || id:ukb-b-533                  MR Egger  135
## 2 Ease of skin tanning || id:ukb-b-533           Weighted median  135
## 3 Ease of skin tanning || id:ukb-b-533 Inverse variance weighted  135
## 4 Ease of skin tanning || id:ukb-b-533               Simple mode  135
## 5 Ease of skin tanning || id:ukb-b-533             Weighted mode  135
##             b          se         pval
## 1 -0.02407673 0.006655542 4.212082e-04
## 2 -0.03166995 0.007739538 4.277255e-05
## 3 -0.02740349 0.005658116 1.277522e-06
## 4 -0.01132845 0.018259404 5.360368e-01
## 5 -0.02440097 0.005274271 8.670713e-06
mr_scatter_plot(d_mr,d)
## $`ukb-b-533.ukb-b-2227`

## 
## attr(,"split_type")
## [1] "data.frame"
## attr(,"split_labels")
##   id.exposure id.outcome
## 1   ukb-b-533 ukb-b-2227
d <- make_dat("ukb-b-2227", "ukb-b-533")
## Extracting data for 3 SNP(s) from 1 GWAS(s)
## Harmonising Number of children fathered || id:ukb-b-2227 (ukb-b-2227) and Ease of skin tanning || id:ukb-b-533 (ukb-b-533)
d_mr<-mr(d)
## Analysing 'ukb-b-2227' on 'ukb-b-533'
d_mr
##   id.exposure id.outcome                              outcome
## 1  ukb-b-2227  ukb-b-533 Ease of skin tanning || id:ukb-b-533
## 2  ukb-b-2227  ukb-b-533 Ease of skin tanning || id:ukb-b-533
## 3  ukb-b-2227  ukb-b-533 Ease of skin tanning || id:ukb-b-533
## 4  ukb-b-2227  ukb-b-533 Ease of skin tanning || id:ukb-b-533
## 5  ukb-b-2227  ukb-b-533 Ease of skin tanning || id:ukb-b-533
##                                       exposure                    method nsnp
## 1 Number of children fathered || id:ukb-b-2227                  MR Egger    3
## 2 Number of children fathered || id:ukb-b-2227           Weighted median    3
## 3 Number of children fathered || id:ukb-b-2227 Inverse variance weighted    3
## 4 Number of children fathered || id:ukb-b-2227               Simple mode    3
## 5 Number of children fathered || id:ukb-b-2227             Weighted mode    3
##            b         se       pval
## 1 -4.4745367 5.70062808 0.57634360
## 2 -0.1861489 0.11601522 0.10859927
## 3 -0.4921385 0.28031132 0.07914214
## 4 -0.1685620 0.10064308 0.23594673
## 5 -0.1544995 0.09382221 0.24136607
mr_scatter_plot(d_mr,d)
## $`ukb-b-2227.ukb-b-533`

## 
## attr(,"split_type")
## [1] "data.frame"
## attr(,"split_labels")
##   id.exposure id.outcome
## 1  ukb-b-2227  ukb-b-533

Skin colour

d <- make_dat("ukb-b-19560", "ukb-b-2227")
## Extracting data for 154 SNP(s) from 1 GWAS(s)
## Finding proxies for 1 SNPs in outcome ukb-b-2227
## Extracting data for 1 SNP(s) from 1 GWAS(s)
## Harmonising Skin colour || id:ukb-b-19560 (ukb-b-19560) and Number of children fathered || id:ukb-b-2227 (ukb-b-2227)
## Removing the following SNPs for incompatible alleles:
## rs111650620, rs137673, rs2094756
d_mr<-mr(d)
## Analysing 'ukb-b-19560' on 'ukb-b-2227'
d_mr
##   id.exposure id.outcome                                      outcome
## 1 ukb-b-19560 ukb-b-2227 Number of children fathered || id:ukb-b-2227
## 2 ukb-b-19560 ukb-b-2227 Number of children fathered || id:ukb-b-2227
## 3 ukb-b-19560 ukb-b-2227 Number of children fathered || id:ukb-b-2227
## 4 ukb-b-19560 ukb-b-2227 Number of children fathered || id:ukb-b-2227
## 5 ukb-b-19560 ukb-b-2227 Number of children fathered || id:ukb-b-2227
##                        exposure                    method nsnp          b
## 1 Skin colour || id:ukb-b-19560                  MR Egger  153 0.02450156
## 2 Skin colour || id:ukb-b-19560           Weighted median  153 0.01148862
## 3 Skin colour || id:ukb-b-19560 Inverse variance weighted  153 0.03754119
## 4 Skin colour || id:ukb-b-19560               Simple mode  153 0.01521776
## 5 Skin colour || id:ukb-b-19560             Weighted mode  153 0.02766040
##            se         pval
## 1 0.010903418 2.608029e-02
## 2 0.013040353 3.783148e-01
## 3 0.009502825 7.797858e-05
## 4 0.036417335 6.766309e-01
## 5 0.008834499 2.090083e-03
mr_scatter_plot(d_mr,d)
## $`ukb-b-19560.ukb-b-2227`

## 
## attr(,"split_type")
## [1] "data.frame"
## attr(,"split_labels")
##   id.exposure id.outcome
## 1 ukb-b-19560 ukb-b-2227
d <- make_dat("ukb-b-2227", "ukb-b-19560")
## Extracting data for 3 SNP(s) from 1 GWAS(s)
## Harmonising Number of children fathered || id:ukb-b-2227 (ukb-b-2227) and Skin colour || id:ukb-b-19560 (ukb-b-19560)
d_mr<-mr(d)
## Analysing 'ukb-b-2227' on 'ukb-b-19560'
d_mr
##   id.exposure  id.outcome                       outcome
## 1  ukb-b-2227 ukb-b-19560 Skin colour || id:ukb-b-19560
## 2  ukb-b-2227 ukb-b-19560 Skin colour || id:ukb-b-19560
## 3  ukb-b-2227 ukb-b-19560 Skin colour || id:ukb-b-19560
## 4  ukb-b-2227 ukb-b-19560 Skin colour || id:ukb-b-19560
## 5  ukb-b-2227 ukb-b-19560 Skin colour || id:ukb-b-19560
##                                       exposure                    method nsnp
## 1 Number of children fathered || id:ukb-b-2227                  MR Egger    3
## 2 Number of children fathered || id:ukb-b-2227           Weighted median    3
## 3 Number of children fathered || id:ukb-b-2227 Inverse variance weighted    3
## 4 Number of children fathered || id:ukb-b-2227               Simple mode    3
## 5 Number of children fathered || id:ukb-b-2227             Weighted mode    3
##             b         se      pval
## 1 3.520696481 2.11750299 0.3447174
## 2 0.072924592 0.07004251 0.2978070
## 3 0.177936009 0.15959752 0.2648913
## 4 0.006810981 0.08078788 0.9404916
## 5 0.030378959 0.08071391 0.7428129
mr_scatter_plot(d_mr,d)
## $`ukb-b-2227.ukb-b-19560`

## 
## attr(,"split_type")
## [1] "data.frame"
## attr(,"split_labels")
##   id.exposure  id.outcome
## 1  ukb-b-2227 ukb-b-19560

Results show that having more childhood sunburn occasions is negatively related with number of children. Ease of tanning is also negatively related. Having darker skin is positively related.

d <- mv_extract_exposures(c("ukb-b-533", "ukb-b-19560"))
## Please look at vignettes for options on running this locally if you need to run many instances of this command.
## Clumping 1, 254 variants, using EUR population reference
## Removing 86 of 254 variants due to LD with other variants or absence from LD reference panel
## Extracting data for 168 SNP(s) from 2 GWAS(s)
## Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Ease of skin tanning || id:ukb-b-533. Just keeping the first instance:
## rs111650620
## Harmonising Ease of skin tanning || id:ukb-b-533 (ukb-b-533) and Skin colour || id:ukb-b-19560 (ukb-b-19560)
## Removing the following SNPs for incompatible alleles:
## rs111650620
## Removing the following SNPs for being palindromic with intermediate allele frequencies:
## rs10771034, rs2591725, rs3894771
o <- extract_outcome_data(d$SNP, "ukb-b-2227")
## Extracting data for 167 SNP(s) from 1 GWAS(s)
## Finding proxies for 1 SNPs in outcome ukb-b-2227
## Extracting data for 1 SNP(s) from 1 GWAS(s)
d <- mv_harmonise_data(d, o)
## Harmonising Ease of skin tanning || id:ukb-b-533 (ukb-b-533) and Number of children fathered || id:ukb-b-2227 (ukb-b-2227)
## Removing the following SNPs for being palindromic with intermediate allele frequencies:
## rs10771034, rs2591725, rs3894771
mv_multiple(d)
## $result
##   id.exposure                             exposure id.outcome
## 1 ukb-b-19560        Skin colour || id:ukb-b-19560 ukb-b-2227
## 2   ukb-b-533 Ease of skin tanning || id:ukb-b-533 ukb-b-2227
##                                        outcome nsnp           b         se
## 1 Number of children fathered || id:ukb-b-2227  129 -0.02930684 0.02451590
## 2 Number of children fathered || id:ukb-b-2227  110 -0.04447047 0.01521875
##          pval
## 1 0.231922420
## 2 0.003476971

Ease of skin tanning is more important.