Note: a that this variable are Blond tresses + blue-eyes regarding 1908 data and you can Blonde tresses + blue/gray attention throughout the 2004 data.
Procedures
, Source van Beijsterveldt, Groen-Blokhuis, Hottenga, Franic, Hudziak and you may Mutton 2013; Willemsen ainsi que al., Site Willemsen, Vink, Abdellaoui, den Braber, van Beek and you can Draisma 2013) have been one of them study in accordance with the presence of worry about-stated investigation on the natural locks and eyes colour plus the presence out-of genotype study on the a keen Illumina 370, 660, 1M or Affymetrix Perlegen-5.0, otherwise six.0 system. There have been seven,063 genotyped Dutch-ancestry people, clustered during the step 3,407 families which have data into vision color, and you can 6,965 genotyped somebody had analysis into the one another locks and eyes colour. On the hereditary organization data of attention color (find Supplementary procedure) most of the research were reviewed. Getting bivariate hereditary analyses within the GCTA, most of the unrelated citizens were picked, according to a hereditary relatedness matrix (GRM) cut-off 0.025 (Yang mais aussi al., Reference Yang, Lee, Goddard and you will Visscher 2011). So it kept step 3,619 someone to the bivariate analyses, which have a genetic relatedness equivalent to below 3rd or fourth relative.
, Resource Willemsen, Vink, Abdellaoui, den Braber, van Beek and you may Draisma 2013). Mature participants said their sheer locks color from a single away from four solutions: ‘fair/blond’, ‘hazel’, ‘red/auburn’, ‘black brown’, and ‘black’ and eyes color which have one of about three possibilities: ‘blue/gray’, ‘green/hazel’ and you can ‘brown’. An identical inquiries toward eyes colour and you may hair color had been answered because of the teenage (14- to help you 18-year-old) twins when they done the new Dutch Health and Choices Survey from inside the 2005 or 2006 (van Beijsterveldt mais aussi al., Reference van Beijsterveldt, Groen-Blokhuis, Hottenga, Franic, Hudziak and you will Lamb 2013). On the statistical analyses, we joint new black colored, light brown, and you will dark brown tresses shade to ‘dark’, given that only not many some body said a black colored locks colour (Lin et al., Source Lin, Mbarek, Willemsen, Dolan, Fedko and you may Abdellaoui 2015). Authored advised concur is actually obtained from every participants.
Decades, gender, absolute tresses, and you will eye color was extracted from Mature NTR questionnaire seven, that has been gathered for the 2004 (Willemsen et al
DNA extraction, purification, and genotype calling of the samples were performed at various points in time following the manufacturer’s protocols and genotype calling programs (Lin et al., Reference Lin, Mbarek, Willemsen, Dolan, Fedko and Abdellaoui 2015). For each platform, the individual SNPs were remapped on the build 37 (HG19), ALL 1000 Genomes Phase 1 imputation reference dataset (Auton et al., Reference Auton, Brooks, Durbin, Garrison, Kang and Korbel 2015). SNPs that failed unique mapping and SNPs with an allele frequency difference over 0.20 with the reference data were removed. SNPs with a minor allele frequency (MAF) < 0.01 were also removed, as well as SNPs that were out of Hardy–Weinberg Equilibrium (HWE) with p < 10 ?5 . The platform data were then merged into a single genotype set and the above SNP QC filters were reapplied. Samples were excluded from the data when their DNA was discordant with their expected sex or IBD status, the genotype missing rate was above 10%, the Plink F-inbreeding value was either larger than 0.10 or smaller than ?0.10, or they were an ethnic outlier based on EIGENSTRAT PCs calculated from the 1000G imputed data (Auton et al., Reference Auton, Brooks, Durbin, Garrison, Kang and Korbel 2015). Phasing of the samples and imputing cross-missing platform SNPs was done with MACH 1 (Li Abecasis, Reference Li and Abecasis 2006). The phased data were then imputed with MINIMAC to the 1000G reference. After imputation, SNPs were filtered, based on Mendelian error rate (>2%), a R 2 imputation quality value of <0.80, MAF <0.01 and a difference of more than 0.15 between the allele frequency and the reference (Howie et al., Reference Howie, Fuchsberger, Stephens, ). We tested the effect of different platforms and removed SNPs showing platform effects. This was done by defining individuals on a specific platform as cases and the others as controls. If the allelic association between the specific platform allele frequency and the other platform's allele frequency was significant (p < 10 ?5 ) SNPs were removed. This left 5,987,253 SNPs, which were all used to construct a GRM.