國家衛生研究院 NHRI:Item 3990099045/12134

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Title:	Genomewide sex-by-snp interaction scan identifies adgrv1 for the sex differences of opioid dependence in african american and supporting evidence in relations with treatment side effects in the asian population
Authors:	Yang, BZ;Zhou, H;Cheng, ZS;Liu, TH;Chung, RH;Kranzler, H;Wang, SC;Farrer, L;Liu, YL;Gelernter, J
Contributors:	Institute of Population Health Sciences;Center for Neuropsychiatric Research
Abstract:	Background: Sex differences in opioid dependence (OD) are in part genetically influenced, but no systematic genomewide search for the relevant genes has been performed. Methods: We conducted genome-wide sex-by-SNP interaction scans using a total of 8,387 subjects (43.6% female), including 2,603 DSM-IV OD African-Americans (AAs) and 2,112 DSM-IV OD European-Americans (EAs). Methadone is a synthetic opioid and is usually used as replacement therapy to treat heroin dependence. We further analyzed a Taiwanese (AS) methadone maintenance treatment (MMT) cohort, including 281 males and 63 females, to support our finding of sex differences in OD. Results: We identified a genome-wide significant (GWS) locus at ADGRV1 (lead of the 9 GWS SNPs, rs2366929 (C/T), p = 1.5 ×10-9) for a differential effect by sex on risk of OD in AAs. This variant influences OD risk in males, but not in females. No GWS variants emerged in EAs. Our finding of sex differences in the association of ADGRV1 with OD was supported by the analysis of the AS MMT cohort. The male sample was used to elucidate the role of the ADGRV1 gene in the OD-related traits. In the AS male sample, the ADGRV1 risk allele rs2366929 ∗C was associated with more severe treatment-emergent symptom scores (TESS) of constipation (FDR adjusted p = 0.003), a symptom usually occurring in long-term opioid use patients and with the TESS scores of irritability (FDR adjusted p = 0.031). In this sample, the CC genotype carriers had higher symptom scores for both constipation and irritability than either the CT or TT genotype carriers. Discussion: ADGRV1 encodes adhesion G protein-coupled receptor V1 and is shown in the GTEx database to be highly expressed in adrenal gland, thyroid, brain (including cau- date and nucleus accumbens), and pituitary gland. No significant sex differences in ADGRV1 expression were observed in GTEx. A Human Phenotype Ontology (HPO) query links ADGRV1 to anxiety, abnormal fear/anxiety-related behavior, and behavioral abnormality. This is the first study to examine the genetic variants contributing to the sex difference in OD systematically. We identified ADGRV1 as GWS contributing to the risk of OD in AA males and treatment-related traits in AS. Further study of these findings is needed.
Date:	2019-08
Relation:	European Neuropsychopharmacology. 2019 Aug;29(Suppl. 4):S1183-S1184.
Link to:	http://dx.doi.org/10.1016/j.euroneuro.2018.08.215
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0924-977X&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000477708400298
Appears in Collections:	[Ren-Hua Chung] Conference Papers/Meeting Abstract [Sheng-Chang Wang] Conference Papers/Meeting Abstract [Yu-Li Liu] Conference Papers/Meeting Abstract

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