Table 2 Top drugs identified using enrichment analysis

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

Drug name

Indication

Smoking trait

Minimal P value and tissue typesa

MAGMAb

Referencec

Putative drug targets that may be repurposed for smoking cessation

Dextromethorphan

Coughing

CigDay

3.3 × 10−39 (caudate basal ganglia)

1.0 × 10−4

32,41

SmkInit

9.2 × 10−15 (brain spinal cord cervical C1)

0.36

SmkCes

2.8 × 10−4 (brain spinal cord cervical C1)

9.2 × 10−9

Ganaxolone

Seizure disorders (investigated)

CigDay

1.3 × 10−9 (substantia nigra)

0.05

33

SmkInit

3.5 × 10−3 (cerebellum)

0.66

SmkCes

0.08 (caudate basal ganglia)

0.02

Galantamine

Alzheimer’s disease

CigDay

4.2 × 10−73 (substantia nigra)

7.7 × 10−14

34,42

SmkInit

1.3 × 10−4 (brain spinal cord cervical C1)

4.3 × 10−3

SmkCes

0.020 (cortex)

3.4 × 10−9

Clinical drugs identified

Nicotine

Smoking cessation

CigDay

4.2 × 10−71 (substantia nigra)

4.3 × 10−17

First-line therapy

SmkInit

1.3 × 10−5 (hypothalamus)

0.01

SmkCes

0.03 (amygdala)

5.8 × 10−11

Varenicline

CigDay

4.8 × 10−26 (frontal cortex BA9)

5.6 × 10−6

First-line therapy

SmkInit

9.2 × 10−15 (brain spinal cord cervical C1)

5.9 × 10−3

SmkCes

2.8×10−4 (brain spinal cord cervical C1)

8.2 × 10−9

Bupropion

CigDay

9.0 × 10−19 (brain spinal cord cervical C1)

0.62

First-line therapy

SmkInit

9.2 × 10−15 (brain spinal cord cervical C1)

0.92

SmkCes

2.8 × 10−4 (brain spinal cord cervical C1)

0.05

Cytisine

CigDay

3.9 × 10−132 (frontal cortex BA9)

5.6 × 10−6

Second-line therapy

SmkInit

9.2 × 10−15 (brain spinal cord cervical C1)

5.9 × 10−3

SmkCes

2.8 × 10−4 (brain spinal cord cervical C1)

8.2 × 10−9

Anxiolytic drugs (butalbital)d

CigDay

4.8 × 10−132 (frontal cortex BA9)

1.1 × 10−3

Second-line therapy

SmkInit

4.9 × 10−5 (cerebellar hemisphere)

7.3 × 10−3

SmkCes

1.1 × 10−3 (caudate basal ganglia)

0.33

  1. Drug enrichment analysis of TESLA results implicates drugs with biological relevance and drugs that are being clinically evaluated. We created gene sets of drug target genes and tested whether these gene sets were enriched with TESLA hits. The most significant TESLA P values for enrichment analysis are shown and, as a comparison and validation, we also show enrichment analysis based on MAGMA for implicated drugs. Full results are available in Supplementary Table 14. All P values are two sided.
  2. aThe minimal P value in 13 brain tissues; significance Bonferroni’s corrected P values that are under 5% threshold and labeled bold.
  3. bMAGMA using the GWAS signals; significant P values after Bonferroni’s correction are labeled bold.
  4. cReferences where the candidate drugs were discussed.
  5. Preliminary clinical/basic evidence/references support the drug repositioning.
  6. dComplete enrichment results for anxiolytic drugs are shown in Supplementary Table 14.
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