Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing

被引：16

作者：

Chen, Fang ^{[1
]}

Wang, Xingyan ^{[1
]}

Jang, Seon-Kyeong ^{[2
]}

Quach, Bryan C. ^{[3
]}

Weissenkampen, J. Dylan ^{[4
,5
]}

Khunsriraksakul, Chachrit ^{[6
]}

Yang, Lina ^{[1
]}

Sauteraud, Renan ^{[1
]}

Albert, Christine M. ^{[7
,8
]}

Allred, Nicholette D. D. ^{[9
]}

Arnett, Donna K. ^{[10
]}

Ashley-Koch, Allison E. ^{[11
,12
,13
]}

Barnes, Kathleen C. ^{[14
]}

Barr, R. Graham ^{[15
]}

Becker, Diane M. ^{[16
,21
]}

Bielak, Lawrence F. ^{[17
]}

Bis, Joshua C. ^{[18
]}

Blangero, John ^{[19
,20
]}

Boorgula, Meher Preethi ^{[14
]}

Chasman, Daniel I.

Chavan, Sameer ^{[14
]}

Chen, Yii-Der I. ^{[22
]}

Chuang, Lee-Ming ^{[23
]}

Correa, Adolfo ^{[24
]}

Curran, Joanne E. ^{[19
]}

David, Sean P. ^{[25
,26
]}

de las Fuentes, Lisa ^{[27
,28
]}

Deka, Ranjan ^{[29
]}

Duggirala, Ravindranath ^{[19
,20
]}

Faul, Jessica D. ^{[30
]}

Garrett, Melanie E. ^{[11
,12
]}

Gharib, Sina A. ^{[18
,31
]}

Guo, Xiuqing ^{[22
]}

Hall, Michael E. ^{[32
]}

Hawley, Nicola L. ^{[33
]}

He, Jiang ^{[34
]}

Hobbs, Brian D. ^{[21
,35
,36
]}

Hokanson, John E. ^{[37
]}

Hsiung, Chao A. ^{[38
]}

Hwang, Shih-Jen ^{[39
,40
]}

Hyde, Thomas M. ^{[41
,42
,43
]}

Irvin, Marguerite R. ^{[44
]}

Jaffe, Andrew E. ^{[41
,42
,45
,46
,47
,48
]}

Johnson, Eric O. ^{[3
]}

Kaplan, Robert ^{[49
,50
]}

Kardia, Sharon L. R.

Kaufman, Joel D. ^{[41
,51
,52
,53
,54
]}

Kelly, Tanika N. ^{[34
]}

Kleinman, Joel E. ^{[42
]}

Kooperberg, Charles ^{[55
]}

机构：

[1] Penn State Coll Med, Dept Publ Hlth Sci, Hershey, PA 17033 USA

[2] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA

[3] RTI Int, Res Triangle Pk, NC USA

[4] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA

[5] Penn State Coll Med, Dept Psychol, Hershey, PA USA

[6] Penn State Coll Med, Dept Bioinformat & Genom, Hershey, PA USA

[7] Cedars Sinai Med Ctr, Dept Cardiol, Los Angeles, CA USA

[8] Brigham & Womens Hosp, Div Prevent Med, Boston, MA USA

[9] Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA

[10] Univ Kentucky, Coll Publ Hlth, Lexington, KY USA

[11] Duke Univ, Duke Mol Physiol Inst, Med Ctr, Durham, NC USA

[12] Duke Univ, Dept Med, Med Ctr, Durham, NC USA

[13] Duke Univ, Duke Comprehens Sickle Cell Ctr, Med Ctr, Durham, NC USA

[14] Univ Colorado, Colorado Ctr Personalized Med, Anschutz Med Ctr, Aurora, CO USA

[15] Columbia Univ, Dept Med, Med Ctr, New York, NY USA

[16] Johns Hopkins Univ, Dept Med, Sch Med, Baltimore, MD USA

[17] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI USA

[18] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA USA

[19] Univ Texas Rio Grande Valley, Dept Human Genet, Sch Med, Brownsville, TX USA

[20] Univ Texas Rio Grande Valley Sch Med, South Texas Diabet & Obes Inst, Brownsville, TX USA

[21] Harvard Med Sch, Boston, MA USA

[22] Harbor UCLA Med Ctr, Lundquist Inst Biomed Innovat, Inst Translat Genom & Populat Sci, Dept Pediat, Torrance, CA USA

[23] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan

[24] Univ Mississippi, Med Ctr, Jackson Heart Study, Dept Med, Jackson, MS USA

[25] Univ Chicago, Chicago, IL USA

[26] NorthShore Univ Hlth Syst, Evanston, IL USA

[27] Washington Univ, Sch Med, Dept Med, Div Biostat, St Louis, MO USA

[28] Washington Univ, Cardiovasc Div, Sch Med, St Louis, MO USA

[29] Univ Cincinnati, Coll Med, Dept Environm & Publ Hlth Sci, Cincinnati, OH USA

[30] Univ Michigan, Survey Res Ctr, Inst Social Res, Ann Arbor, MI USA

[31] Univ Washington, Comp Med Core Ctr Lung Biol, Div Pulm Crit Care & Sleep Med, Seattle, WA USA

[32] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS USA

[33] Yale Univ, Sch Publ Hlth, Dept Epidemiol Chron Dis, New Haven, CT USA

[34] Tulane Univ, Dept Epidemiol, Sch Publ Hlth & Trop Med, New Orleans, LA USA

[35] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA

[36] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA USA

[37] Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Anschutz Med Campus, Aurora, CO USA

[38] Natl Hlth Res Inst, Colorado Sch Publ Hlth, Dept Epidemiol, Anschutz Med Campus, Aurora, CO USA

[39] NIH, Natl Heart Lung & Blood Inst, Div Intramural Res, Populat Sci Branch, Bethesda, MD USA

[40] Framingham Heart Dis Epidemiol Study, Framingham, MA USA

[41] Lieber Inst Brain Dev, Baltimore, MD USA

[42] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Sch Med, Baltimore, MD USA

[43] Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD USA

[44] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA

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

[46] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA

[47] Johns Hopkins Univ, Sch Med, Dept Human Genet, Baltimore, MD USA

[48] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD USA

[49] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, The Bronx, NY USA

[50] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA USA

来源：

NATURE GENETICS | 2023年 / 55卷 / 02期

基金：

美国国家卫生研究院;

关键词：

GENERAL FRAMEWORK; RARE VARIANTS; CEREBELLUM; NICOTINE;

D O I：

10.1038/s41588-022-01282-x

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods. When applied to tobacco use phenotypes, TESLA identified 273 new genes, up to 55% more compared with alternative TWAS methods. These hits and subsequent fine mapping using TESLA point to target genes with biological relevance. In silico drug-repurposing analyses highlight several drugs with known efficacy, including dextromethorphan and galantamine, and new drugs such as muscle relaxants that may be repurposed for treating nicotine addiction.

引用

页码：291 / +

页数：15

共 28 条

[1] Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing
Fang Chen
Xingyan Wang
Seon-Kyeong Jang
Bryan C. Quach
J. Dylan Weissenkampen
Chachrit Khunsriraksakul
Lina Yang
Renan Sauteraud
Christine M. Albert
Nicholette D. D. Allred
Donna K. Arnett
Allison E. Ashley-Koch
Kathleen C. Barnes
R. Graham Barr
Diane M. Becker
Lawrence F. Bielak
Joshua C. Bis
John Blangero
Meher Preethi Boorgula
Daniel I. Chasman
Sameer Chavan
Yii-Der I. Chen
Lee-Ming Chuang
Adolfo Correa
Joanne E. Curran
Sean P. David
Lisa de las Fuentes
Ranjan Deka
Ravindranath Duggirala
Jessica D. Faul
Melanie E. Garrett
Sina A. Gharib
Xiuqing Guo
Michael E. Hall
Nicola L. Hawley
Jiang He
Brian D. Hobbs
John E. Hokanson
Chao A. Hsiung
Shih-Jen Hwang
Thomas M. Hyde
Marguerite R. Irvin
Andrew E. Jaffe
Eric O. Johnson
Robert Kaplan
Sharon L. R. Kardia
Joel D. Kaufman
Tanika N. Kelly
Joel E. Kleinman
Charles Kooperberg
[J]. Nature Genetics, 2023, 55 (2) : 291 - 300
[2] METRO: Multi-ancestry transcriptome-wide association studies for powerful gene-trait association detection
Li, Zheng
Zhao, Wei
Shang, Lulu
Mosley, Thomas H.
Kardia, Sharon L. R.
Smith, Jennifer A.
Zhou, Xiang
[J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2022, 109 (05) : 783 - 801
[3] A multi-ancestry cerebral cortex transcriptome-wide association study identifies genes associated with smoking behaviors
Tan, Qilong
Xu, Xiaohang
Zhou, Hanyi
Jia, Junlin
Jia, Yubing
Tu, Huakang
Zhou, Dan
Wu, Xifeng
[J]. MOLECULAR PSYCHIATRY, 2024,
[4] Multi-ancestry fine-mapping improves precision to identify causal genes in transcriptome-wide association studies
Lu, Zeyun
Gopalan, Shyamalika
Yuan, Dong
Conti, David, V
Pasaniuc, Bogdan
Gusev, Alexander
Mancuso, Nicholas
[J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2022, 109 (08) : 1388 - 1404
[5] MULTI-ANCESTRY PHENOME-WIDE ASSOCIATION ANALYSES OF GENETIC LIABILITY FOR PROBLEMATIC ALCOHOL USE
Kember, Rachel
Johnson, Jessica
Johnston, Keira J. A.
Lee, Hyunjoon
Xu, Jiayi
Davis, Lea K.
Smoller, Jordan W.
Mallard, Travis T.
Huckins, Laura M.
Sanchez-Roige, Sandra
Kranzler, Henry R.
Gelernter, Joel
Zhou, Hang
[J]. EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2023, 75 : S10 - S10
[6] Transcriptome-wide association study of treatment-resistant depression for drug repurposing
Fabbri, C.
Pain, O.
Hagenaars, S.
Lewis, C.
Serretti, A.
[J]. EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2021, 53 : S263 - S264
[7] MATS: a novel multi-ancestry transcriptome-wide association study to account for heterogeneity in the effects of cis-regulated gene expression on complex traits
Knutson, Katherine A.
Pan, Wei
[J]. HUMAN MOLECULAR GENETICS, 2023, 32 (08) : 1237 - 1251
[8] Transcriptome-wide association study of treatment-resistant depression and depression subtypes for drug repurposing
Fabbri, Chiara
Pain, Oliver
Hagenaars, Saskia P.
Lewis, Cathryn M.
Serretti, Alessandro
[J]. NEUROPSYCHOPHARMACOLOGY, 2021, 46 (10) : 1821 - 1829
[9] Transcriptome-wide association study of treatment-resistant depression and depression subtypes for drug repurposing
Chiara Fabbri
Oliver Pain
Saskia P. Hagenaars
Cathryn M. Lewis
Alessandro Serretti
[J]. Neuropsychopharmacology, 2021, 46 : 1821 - 1829
[10] TRANSCRIPTOME-WIDE ASSOCIATION STUDY OF TREATMENT-RESISTANT DEPRESSION AND DEPRESSION SUBTYPES FOR DRUG REPURPOSING
Fabbri, Chiara
Pain, Oliver
Hagenaars, Saskia
Lewis, Cathryn
Serretti, Alessandro
[J]. EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2021, 51 : E8 - E9

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