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Association between genetic risk scores and risk of narcolepsy: a case-control study.

ABSTRACT: Background:Genome-wide association studies (GWASs) have identified a large number of single-nucleotide polymorphisms (SNPs) associated with narcolepsy. However, the sum impact of these SNPs on defining the genomic risk of narcolepsy remains unknown. In the present study, we investigated the associations between genetic risk scores (GRSs) and narcolepsy along with their predictive power. Methods:A case-control study consisting of 903 narcolepsy patients and 1,981 healthy control subjects was performed. Thirty-two SNPs previously reported to confer susceptibility to narcolepsy were assessed for their association with narcolepsy risk. Subsequently, we constructed four GRS groups comprising reported narcolepsy susceptibility SNPs located in different genomic regions, and tested their association with narcolepsy risk using a regression model. Receiver operating characteristic (ROC) curves were used to examine the discriminatory power of the GRSs for predicting narcolepsy. Results:Nine individual SNPs were significantly associated with narcolepsy after Bonferroni correction. All four GRSs were strongly associated with narcolepsy risk even when GRSs were constructed using SNPs located outside the previously implicated human leukocyte antigen (HLA) region on chromosome 6. The odds ratio (OR) for narcolepsy risk increased with the number of genetic loci implicated, ranging from an OR of 2.016 (95% CI, 1.657-2.456) to an OR of 4.298 (95% CI, 3.378-5.481). GRS4, constructed using the narcolepsy-associated SNPs identified in the Chinese population, was most closely associated with narcolepsy risk. Conclusions:The results suggest that the GRS method for combining common genetic variations can significantly associate GRS scores with narcolepsy risk and may facilitate narcolepsy risk stratification for prevention trials, both for HLA-DQB1*06:02-positive and -negative individuals.

SUBMITTER: Ouyang H

PROVIDER: S-EPMC7048986 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Association between genetic risk scores and risk of narcolepsy: a case-control study.

Ouyang Hui H Han Fang F Zhou Zechen Z Zheng Qiwen Q Wang Yangyang Y Zhang Jun J

Annals of translational medicine 20200201 4

<h4>Background</h4>Genome-wide association studies (GWASs) have identified a large number of single-nucleotide polymorphisms (SNPs) associated with narcolepsy. However, the sum impact of these SNPs on defining the genomic risk of narcolepsy remains unknown. In the present study, we investigated the associations between genetic risk scores (GRSs) and narcolepsy along with their predictive power.<h4>Methods</h4>A case-control study consisting of 903 narcolepsy patients and 1,981 healthy control su ...[more]

PMID: 32175396

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Project description:BackgroundGastrointestinal cancer, such as gastric, colon and rectal cancer, is a major medical and economic burden worldwide. However, the exact mechanism of gastrointestinal cancer development still remains unclear. RAS genes have been elucidated as major participants in the development and progression of a series of human tumours and the single nucleotide polymorphism at H-RAS cDNA position 81 was demonstrated to contribute to the risks of bladder, oral and thyroid carcinoma. Therefore, we hypothesized that this polymorphisms in H-RAS could influence susceptibility to gastrointestinal cancer as well, and we conducted this study to test the hypothesis in Chinese population.MethodsA population based case-control study, including 296 cases with gastrointestinal cancer and 448 healthy controls selected from a Chinese population was conducted. H-RAS T81C polymorphism was genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay.ResultsIn the healthy controls, the TT, TC and CC genotypes frequencies of H-RAS T81C polymorphism, were 79.24%, 19.87% and 0.89%, respectively, and the C allele frequency was 10.83%. Compared with TT genotype, the TC genotype was significantly associated with an increased risk of gastric cancer (adjusted OR = 3.67, 95%CI = 2.21-6.08), while the CC genotype showed an increased risk as well (adjusted OR = 3.29, 95%CI = 0.54-19.86), but it was not statistically significant. In contrast, the frequency of TC genotype was not significantly increased in colon cancer and rectal cancer patients. Further analysis was performed by combining TC and CC genotypes compared against TT genotype. As a result, a statistically significant risk with adjusted OR of 3.65 (95%CI, 2.22-6.00) was found in gastric cancer, while no significant association of H-RAS T81C polymorphism with colon cancer and rectal cancer was observed.ConclusionThese findings indicate, for the first time, that there is an H-RAS T81C polymorphism existing in Chinese population, and this SNP might be a low penetrance gene predisposition factor for gastric cancer.

Dataset Information

Association between genetic risk scores and risk of narcolepsy: a case-control study.

Publications

Association between genetic risk scores and risk of narcolepsy: a case-control study.

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