A global reference for human genetic variation.
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Cites background from "A global reference for human geneti..."
...We find that on average, 3.1% of the 2,504 individuals in the 1000 Genomes Project carry at least one allele with a missense variation in a known functional site in any given GPCR drug target (11.9% in known or putative functional site; Table S5)....
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...Fraction of receptor length with a polymorphism or population with variant receptor For each of theGPCRdrug targets we calculated: (i) the ratio of receptor length withmissense variation in a known functional sites per GPCR drug target using the ExAC data (Table S5) and (ii) the fraction of affected individuals in the human population (n = 2,504; based on the 1000 Genomes Project dataset, Table S5)....
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...2012 and 2017 have partial sales data and were not considered. d %Individuals is the percentage of affected individuals with amissense variant in a functional site of the respective drug target(s) (n = 2,504 individuals from 1000 Genomes Project genotype data as a representative for the UK population; this data includes non-Caucasian populations as well) (Table S5). d The % of affected individuals was calculated using four different criteria by considering individuals who have a variation in (i) known functional sites in both alleles (homozygous), which is the most conservative, (ii) known functional sites in at least one allele (i.e., homozygous and heterozygous), (iii) known or putative functional sites in both alleles (homozygous), and (iv) known or putative functional sites in at least one allele (i.e., homozygous and heterozygous), which is the least conservative. d Known functional sites include ligand binding, effector binding, post-translational modification site, sodium binding site and micro-switches....
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...An investigation of complete genotype information for 2,504 ‘‘healthy’’ individuals from the 1000 Genomes Project (Auton et al., 2015) showed that, on average, an individual harbors 68 missense variations within the coding region of one-third of the GPCR drug targets (Figure 2A)....
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...=X fraction of known functional sites that are polymorphic for each receptor targeted by the drug The drug score (Table S6) based on prevalence of affected individual (i.e., 1000 Genomes Project) was calculated by: variability score for a drug;Saffected% = fraction of affected individuals with a MV in a functional site of the respective drug targetðsÞ The fraction of affected individuals was calculated using four different criteria by considering individuals who have a variation in (i) known functional sites in both alleles (homozygous), which is the most conservative, (ii) known functional sites in at least one allele (i.e., homozygous and heterozygous), (iii) known or putative functional sites in both alleles (homozygous), and (iv) known or putative functional sites in at least one allele (i.e., homozygous and heterozygous), which is the least conservative....
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408 citations
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Cites methods from "A global reference for human geneti..."
...To do so, we first calculated FST values between the Yoruba African (YRI) and the western European population (CEU) in Phase 3 data from the 1000 Genomes Project (Auton et al., 2015)....
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...Bi-allelic SNPs across five European population samples (CEU, FIN, GBR, IBS, TSI), three African population samples with low levels of Eurasian ancestry (ESN, MSL, YRI), and ancestral allele were extracted from the phase 3 release of the 1,000 Genomes Project....
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...The prior genotype probabilities in QuASAR are obtained from the 1000 Genomes Project minor allele frequencies assuming Hardy–Weinberg equilibrium; however, as we had the genotype information available, we manually input the prior genotype probabilities....
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400 citations
References
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