PMID- 32175396
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220413
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 8
IP  - 4
DP  - 2020 Feb
TI  - Association between genetic risk scores and risk of narcolepsy: a case-control 
      study.
PG  - 103
LID - 10.21037/atm.2019.12.95 [doi]
LID - 103
AB  - 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.
CI  - 2020 Annals of Translational Medicine. All rights reserved.
FAU - Ouyang, Hui
AU  - Ouyang H
AD  - Department of Neuromedicine, Peking University People's Hospital, Beijing 100044, 
      China.
FAU - Han, Fang
AU  - Han F
AD  - Department of Pulmonary Medicine, Peking University People's Hospital, Beijing 
      100044, China.
FAU - Zhou, Zechen
AU  - Zhou Z
AD  - Department of Epidemiology and Biostatistics, School of Public Health, Peking 
      University Health Science Center, Beijing 100191, China.
FAU - Zheng, Qiwen
AU  - Zheng Q
AD  - Department of Epidemiology and Biostatistics, School of Public Health, Peking 
      University Health Science Center, Beijing 100191, China.
FAU - Wang, Yangyang
AU  - Wang Y
AD  - Department of Neuromedicine, Peking University People's Hospital, Beijing 100044, 
      China.
FAU - Zhang, Jun
AU  - Zhang J
AD  - Department of Neuromedicine, Peking University People's Hospital, Beijing 100044, 
      China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC7048986
OTO - NOTNLM
OT  - Case-control study
OT  - genetic risk score (GRS)
OT  - single-nucleotide polymorphisms (SNPs)
COIS- Conflicts of Interest: The authors have no conflicts of interest to declare.
EDAT- 2020/03/17 06:00
MHDA- 2020/03/17 06:01
PMCR- 2020/02/01
CRDT- 2020/03/17 06:00
PHST- 2020/03/17 06:00 [entrez]
PHST- 2020/03/17 06:00 [pubmed]
PHST- 2020/03/17 06:01 [medline]
PHST- 2020/02/01 00:00 [pmc-release]
AID - atm-08-04-103 [pii]
AID - 10.21037/atm.2019.12.95 [doi]
PST - ppublish
SO  - Ann Transl Med. 2020 Feb;8(4):103. doi: 10.21037/atm.2019.12.95.