Olfactory Receptor Gene Polymorphisms and Nonallergic Vasomotor Rhinitis

Abstract

We sought a genotype-phenotype association: between single-nucleotide polymorphisms (SNPs) in olfactory receptor (OR) genes from the two largest OR gene clusters and odor-triggered nonallergic vasomotor rhinitis (nVMR). In the initial pedigree screen, using transmission disequilibrium test (TDT) analysis, six SNPs showed "significant" p-values between 0.0449 and 0.0043. In a second case-control population, the previously identified six SNPs did not re-emerge, whereas four new SNPs showed p-values between 0.0490 and 0.0001. Combining both studies, none of the SNPs in the TDT analysis survived the Bonferroni correction. In the population study, one SNP showed an empirical p-value of 0.0066 by shuffling cases and controls with 10 5 replicates; however, the p-value for this SNP was 0.83 in the pedigree study. This study emphasizes that underpowered studies having p-values between <0.05 and 0.0001 should be regarded as inconclusive and require further replication before concluding the study is "informative." However, we believe that our hypothesis that an association between OR genotypes and the nVMR phenotype remains feasible. Future studies using either a genomewide association study of all OR gene-pseudogene regions throughout the genome -at the current recommended density of 2.5 to 5 kb per tag SNP-or studies incorporating microarray analyses of the entire "OR genome" in well-characterized nVMR patients are required.

Critical Association Study of Olfactory Receptor Gene Polymorphism in Diabetic Complications

“…The study provided strong genetic confirmation for already existing reports about the unique appearance of OR that is inextricably related to immunological function [20][21][22]. In addition, it might be an interesting genetic reasoning for the accumulative evidence that OR dysfunction exists in brain diseases such as Multiple Sclerosis [23][24][25][26][27][28][29] OR14 gene is located in the telomeric region of HLA-F [14] where an interesting haplotype-specific association between T1D and a SNP in the promoter region of OR14 gene, rs9257691, has been reported [14].…”

Head-and-neck squamous cell carcinoma risk in smokers: no association detected between phenotype and AHR, CYP1A1, CYP1A2, or CYP1B1 genotype

“…Using the chi-square test for allele-frequency difference of each tag-SNP between HS and HR samples (Table 3), we found three P values significant at the P  < 0.05 level; however, these associations did not retain statistical significance in the 100,000 permutations test. This is a very common observation and often not appreciated—when comparing standard statistical tests with a permutation test that is mandatory for association studies with regard to multiple markers throughout all chromosomes [4]. …”

“…Also, in contrast to the present study that used the EDP method of sample selection, all the studies mentioned above used, as their control population—nonsmokers, or any smoker not having cancer. Furthermore, none of these studies employed any form of multi-locus statistical testing; this is a very serious recurring problem in the medical literature with regard to studies attempting to discover associations between one or more SNPs and a multifactorial trait [4, 36], which is a type I (false-positive) error variously called “ P  < 0.05 studies” [36] and the “incidentalome” [18]. …”

Omics Screening for Pharmaceutical Efficacy and Safety in Clinical Practice

“…These projects provide resources for investigators to make large-scale genome level associations. These “genome wide association” (GWA) studies require extremely large sample sizes to reach statistical significance [7]. GWA studies have attempted to provide screening tests for medication-induced toxicity.…”