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

被引：29

作者：

Gaddis, Nathan ^{[1
]}

Mathur, Ravi ^{[1
]}

Marks, Jesse ^{[1
]}

Zhou, Linran ^{[1
]}

Quach, Bryan ^{[1
]}

Waldrop, Alex ^{[1
]}

Levran, Orna ^{[2
]}

Agrawal, Arpana ^{[3
]}

Randesi, Matthew ^{[2
]}

Adelson, Miriam ^{[4
]}

Jeffries, Paul W. ^{[3
]}

Martin, Nicholas G. ^{[5
]}

Degenhardt, Louisa ^{[6
]}

Montgomery, Grant W. ^{[7
]}

Wetherill, Leah ^{[8
]}

Lai, Dongbing ^{[8
]}

Bucholz, Kathleen ^{[3
]}

Foroud, Tatiana ^{[8
]}

Porjesz, Bernice ^{[9
]}

Runarsdottir, Valgerdur ^{[10
]}

Tyrfingsson, Thorarinn ^{[10
]}

Einarsson, Gudmundur ^{[11
]}

Gudbjartsson, Daniel F. ^{[11
]}

Webb, Bradley Todd ^{[1
]}

Crist, Richard C. ^{[12
]}

Kranzler, Henry R. ^{[12
]}

Sherva, Richard ^{[27
]}

Zhou, Hang ^{[13
]}

Hulse, Gary ^{[14
]}

Wildenauer, Dieter ^{[14
]}

Kelty, Erin ^{[15
]}

Attia, John ^{[16
]}

Holliday, Elizabeth G. ^{[16
,17
]}

McEvoy, Mark ^{[16
,17
]}

Scott, Rodney J. ^{[18
]}

Schwab, Sibylle G. ^{[19
]}

Maher, Brion S. ^{[20
]}

Gruza, Richard ^{[21
]}

Kreek, Mary Jeanne ^{[2
]}

Nelson, Elliot C. ^{[3
]}

Thorgeirsson, Thorgeir ^{[11
]}

Stefansson, Kari ^{[11
,22
]}

Berrettini, Wade H. ^{[12
]}

Gelernter, Joel ^{[23
]}

Edenberg, Howard J. ^{[24
]}

Bierut, Laura ^{[25
]}

Hancock, Dana B.

Johnson, Eric Otto ^{[1
,26
]}

机构：

[1] RTI Int, Biostat & Epidemiol Div, GenOm Bioinformat & Translat Res Ctr, Res Triangle Pk, NC 27709 USA

[2] Rockefeller Univ, Lab Biol Addict Dis, 1230 York Ave, New York, NY 10021 USA

[3] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[4] Dr Miriam & Sheldon G Adelson Clin Drug Abuse Tre, Las Vegas, NV USA

[5] QIMR Berghofer Med Res Inst, Genet Epidemiol, Brisbane, Qld, Australia

[6] Univ New South Wales, Natl Drug & Alcohol Res Ctr, Randwick, NSW, Australia

[7] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia

[8] Indiana Univ Sch Med, Med & Mol Genet, Indianapolis, IN 46202 USA

[9] Suny Downstate Med Ctr, Dept Psychiat, Brooklyn, NY 11203 USA

[10] Vogur Hosp, SAA Natl Ctr Addict Med, Reykjavik, Iceland

[11] deCODE Genet Amgen, Reykjavik, Iceland

[12] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA

[13] Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06516 USA

[14] Univ Western Australia, Sch Psychiat & Clin Neurosci, Perth, WA, Australia

[15] Univ Western Australia, Sch Populat & Global Hlth, Populat & Publ Hlth, Perth, WA, Australia

[16] Hunter Med Res Inst, Newcastle, NSW, Australia

[17] Univ Newcastle, Sch Med & Publ Hlth, Coll Hlth Med & Wellbeing, Callaghan, NSW, Australia

[18] Univ Newcastle, Sch Biomed Sci & Pharm, Coll Hlth Med & Wellbeing, New Lambton Hts, NSW, Australia

[19] Univ Wollongong, Fac Sci Med & Hlth, Wollongong, NSW, Australia

[20] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA

[21] St Louis Univ, Dept Family & Community Med, St Louis, MO 63103 USA

[22] Univ Iceland, Fac Med, Reyjavik, Iceland

[23] Yale Univ, Sch Med, Dept Psychiat Genet & Neurosci, West Haven, CT 06516 USA

[24] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA

[25] Washington Univ, Dept Psychiat, St Louis, MO USA

[26] RTI Int, Fellow Program, Res Triangle Pk, NC 27709 USA

[27] Boston Univ, Genome Sci Inst, Boston, MA 02215 USA

来源：

SCIENTIFIC REPORTS | 2022年 / 12卷 / 01期

基金：

欧盟地平线“2020”; 美国国家卫生研究院;

关键词：

HEROIN-ADDICTION; UNITED-STATES; RISK; DEPENDENCE; EFFICIENT; DRUG; METAANALYSIS; CONTRIBUTE; GENETICS; OVERDOSE;

D O I：

10.1038/s41598-022-21003-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Opioid addiction (OA) is moderately heritable, yet 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 together with 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 (r(g) > 0.9). We observed the strongest evidence to date for OPRM1: lead SNP rs9478500 (p = 2.56 x 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.

引用

页数：16

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