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

Publication ,  Journal Article
Chen, F; Wang, X; Jang, S-K; Quach, BC; Weissenkampen, JD; Khunsriraksakul, C; Yang, L; Sauteraud, R; Albert, CM; Allred, NDD; Arnett, DK ...
Published in: Nat Genet
February 2023

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.

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Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

February 2023

Volume

55

Issue

2

Start / End Page

291 / 300

Location

United States

Related Subject Headings

  • Transcriptome
  • Tobacco Use
  • Polymorphism, Single Nucleotide
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Drug Repositioning
  • Developmental Biology
  • Biology
  • 3105 Genetics
 

Citation

APA
Chicago
ICMJE
MLA
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Chen, F., Wang, X., Jang, S.-K., Quach, B. C., Weissenkampen, J. D., Khunsriraksakul, C., … Liu, D. J. (2023). Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing. Nat Genet, 55(2), 291–300. https://doi.org/10.1038/s41588-022-01282-x
Chen, Fang, Xingyan Wang, Seon-Kyeong Jang, Bryan C. Quach, J Dylan Weissenkampen, Chachrit Khunsriraksakul, Lina Yang, et al. “Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing.Nat Genet 55, no. 2 (February 2023): 291–300. https://doi.org/10.1038/s41588-022-01282-x.
Chen F, Wang X, Jang S-K, Quach BC, Weissenkampen JD, Khunsriraksakul C, et al. Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing. Nat Genet. 2023 Feb;55(2):291–300.
Chen, Fang, et al. “Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing.Nat Genet, vol. 55, no. 2, Feb. 2023, pp. 291–300. Pubmed, doi:10.1038/s41588-022-01282-x.
Chen F, Wang X, Jang S-K, Quach BC, Weissenkampen JD, Khunsriraksakul C, Yang L, Sauteraud R, Albert CM, Allred NDD, Arnett DK, Ashley-Koch AE, Barnes KC, Barr RG, Becker DM, Bielak LF, Bis JC, Blangero J, Boorgula MP, Chasman DI, Chavan S, Chen Y-DI, Chuang L-M, Correa A, Curran JE, David SP, Fuentes LDL, Deka R, Duggirala R, Faul JD, Garrett ME, Gharib SA, Guo X, Hall ME, Hawley NL, He J, Hobbs BD, Hokanson JE, Hsiung CA, Hwang S-J, Hyde TM, Irvin MR, Jaffe AE, Johnson EO, Kaplan R, Kardia SLR, Kaufman JD, Kelly TN, Kleinman JE, Kooperberg C, Lee I-T, Levy D, Lutz SM, Manichaikul AW, Martin LW, Marx O, McGarvey ST, Minster RL, Moll M, Moussa KA, Naseri T, North KE, Oelsner EC, Peralta JM, Peyser PA, Psaty BM, Rafaels N, Raffield LM, Reupena MS, Rich SS, Rotter JI, Schwartz DA, Shadyab AH, Sheu WH-H, Sims M, Smith JA, Sun X, Taylor KD, Telen MJ, Watson H, Weeks DE, Weir DR, Yanek LR, Young KA, Young KL, Zhao W, Hancock DB, Jiang B, Vrieze S, Liu DJ. Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing. Nat Genet. 2023 Feb;55(2):291–300.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

February 2023

Volume

55

Issue

2

Start / End Page

291 / 300

Location

United States

Related Subject Headings

  • Transcriptome
  • Tobacco Use
  • Polymorphism, Single Nucleotide
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Drug Repositioning
  • Developmental Biology
  • Biology
  • 3105 Genetics