Multi-trait genome-wide association study of opioid addiction: OPRM1 and Beyond-Reference-Cited by-同舟云学术

Multi-trait genome-wide association study of opioid addiction: OPRM1 and Beyond

Published:2021-09-16 Issue: Volume: Page:
ISSN:
Container-title:
language:
Short-container-title:

Author:

Gaddis Nathan,Mathur Ravi^ORCID,Marks Jesse^ORCID,Zhou Linran,Quach Bryan^ORCID,Waldrop Alex,Levran Orna^ORCID,Agrawal Arpana^ORCID,Randesi Matthew^ORCID,Adelson Miriam,Jeffries Paul W.,Johnson Emma C.^ORCID,Martin Nicholas G.^ORCID,Degenhardt Louisa^ORCID,Montgomery Grant W^ORCID,Wetherill Leah^ORCID,Lai Dongbing^ORCID,Bucholz Kathleen^ORCID,Foroud Tatiana^ORCID,Porjesz Bernice^ORCID,Webb Bradley Todd,Crist Richard C.^ORCID,Kranzler Henry R.,Zhou Hang,Hulse Gary^ORCID,Wildenauer Dieter^ORCID,Kelty Erin^ORCID,Attia John^ORCID,Holliday Elizabeth G.^ORCID,McEvoy Mark^ORCID,Scott Rodney J.^ORCID,Schwab Sibylle G^ORCID,Maher Brion S.^ORCID,Gruza Richard,Kreek Mary-Jeanne^ORCID,Nelson Elliot C.^ORCID,Berrettini Wade H.^ORCID,Gelernter Joel^ORCID,Edenberg Howard^ORCID,Bierut Laura,Hancock Dana B.,Johnson Eric O.^ORCID

Abstract

AbstractOpioid addiction (OA) has strong heritability, yet few genetic variant associations have been robustly identified. Only rs1799971, the A118G variant in OPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data and published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry. Genetic correlations among the various OA phenotypes were uniformly high (rg > 0.9). We observed the strongest evidence to date for OPRM1: lead SNP rs9478500 (p=2.56×10−9). Gene-based analyses identified novel genome-wide significant associations with PPP6C and FURIN. Variants within these loci appear to be pleiotropic for addiction and related traits.

Publisher

Cold Spring Harbor Laboratory

Reference76 articles.

1. Ahmad, F.B. , Rossen, L.M. & Sutton, P. Provisional drug overdose death counts. (National Center for Health Statistics, 2021).

2. Increases in Drug and Opioid Overdose Deaths — United States, 2000–2014

3. National Safety Council. Motor vehicle deaths estimated to have dropped 2% in 2019. (2020).

4. Substance Abuse and Mental Health Services Administration. Key substance use and mental health indicators in the United States: Results from the 2019 National Survey on Drug Use and Health (HHS Publication No. PEP20-07-01-001, NSDUH Series H-55). (Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration., Rockville, MD, 2020).

5. The Economic Burden of Prescription Opioid Overdose, Abuse, and Dependence in the United States, 2013

Cited by 7 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Genome‐wide analyses reveal novel opioid use disorder loci and genetic overlap with schizophrenia, bipolar disorder, and major depression;Addiction Biology;2023-04-28

2. Multi-trait genome-wide association analyses leveraging alcohol use disorder findings identify novel loci for smoking behaviors in the Million Veteran Program;2022-10-21

3. Genome-wide analyses reveal novel opioid use disorder loci and genetic overlap with schizophrenia, bipolar disorder, and major depression;2022-09-09

4. Genome-wide association study in individuals of European and African ancestry and multi-trait analysis of opioid use disorder identifies 19 independent genome-wide significant risk loci;Molecular Psychiatry;2022-07-25

5. CADM2is implicated in impulsive personality and numerous other traits by genome- and phenome-wide association studies in humans and mice;2022-01-31