Computational protocol: The relationship between dopamine receptor D1 and cognitive performance

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Protocol publication

[…] DNA from the LOGOS cohort was extracted from blood or cheek swab samples, using the QIAamp DNA Blood Mini Kit (Qiagen, Hilden, Germany). Genotyping of DRD1 rs5326 was performed blind to phenotype measures by LGC Genomics (Herts, UK) (http://www.lgcgenomics.com/) with a competitive, allele-specific PCR system. The call rate for rs5326 was 98.46% and genotype frequencies were distributed in accordance with Hardy–Weinberg equilibrium (χ2 =0.35; P=0.56). Genotyping quality control for each SNP was performed in 50 randomly selected samples by duplicate checking (rate of concordance in duplicates >99%). All the subjects were of Caucasian ancestry on the basis of self-report, which was confirmed for a subset of the cohort (833 out of 840 subjects) on the basis of EIGENSOFT analysis, of genome-wide genotyping SNP profiling with the Illumina HumanOmniExpress BeadChip (San Diego, CA, USA). On the basis of these data, the self-report identification of the Caucasian ancestry is 99.2% (833/840) reliable, which makes genetic inhomogeneity of the tested population unlikely. [...] The preprocessing of SNP data and genetic analysis was performed with Plink (Version 1.07). More specifically, individuals were removed if they were outliers with respect to estimated heterozygosity (more than 3 s.d.) or had missing SNPs >5%. SNPs were removed if: missing genotype rate >5%; Hardy–Weinberg equilibrium P<10−3, minor allele frequency <5%. For any pair of subjects with cryptic relatedness (pi-hat >0.125 in PLINK, the sample with the lower call rate was eliminated. After QC, we had genotype profiling for 1,093 SNPs in 727 individuals (148 controls, 349 cases with AD, and 230 cases with schizophrenia) with total genotyping rate 99.9%. All the subjects were of Caucasian ancestry on the basis of self-report, which was confirmed for a subset of the cohort (310 out of 318 subjects or 97.5%) on the basis of EIGENSOFT analysis, of genome-wide genotyping SNP profiling using the Affymetrix SNP 6.0 array (Santa Clara, CA, USA). We used a linear regression model to examine the association of CDR and genotypes across diagnostic groups:CDR=β0+βGG+βSexSex+βAgeAge+βSczScz+βADAD+βG×SczGScz+βG×ADGAD,where β G is the parameter of interest quantifying the association between a genotype G and the mean of CDR controlling for sex, age, disease status—schizophrenia (Scz) and AD, and disease by genotype interaction for schizophrenia (G×Scz) and AD (G×AD). To correct for multiple testing and reduce the probability of type I error, empirical P values (P emp) were estimated on the basis of 100,000 permutations. […]

Pipeline specifications

Software tools EIGENSOFT, PLINK
Applications Population genetic analysis, GWAS
Organisms Homo sapiens
Diseases Alzheimer Disease, Dementia, Neuroblastoma
Chemicals Dopamine