Table 1 High confidence genes associated with aging phenotypes (TWAS significant, conditionally significant, and PIP > 0.5)

From: Multi-omic underpinnings of epigenetic aging and human longevity

Phenotype

Gene

Novel

TWAS Z score

FOCUS PIP

Joint P value (conditional analysis)

PP.H4 (colocalization analysis)

Permutation test P value

HannumAge

ZNF37A

NO

7.80

1.00

5.30 × 10−7

0.042

0.050

FLOT1

YES

−5.83

0.67

3.30 × 10−7

1.00

0.002

KPNA4

YES

−4.97

0.83

6.90 × 10−7

0.96

0.002

ZNF248

NO

6.05

1.00

2.40 × 10−18

0.00

0.30

ENSG00000245156

NO

−5.33

0.97

9.70 × 10−8

0.88

0.008

GrimAge

SESN1

NO

−4.85

0.91

1.20 × 10−6

0.94

0.022

ENSG00000272540

NO

5.00

0.72

5.60 × 10−7

0.87

0.005

IEAA

CD46

NO

−5.80

1.00

6.60 × 10−9

0.51

0.020

TPMT

NO

−11.50

1.00

9.20 × 10−16

0.007

0.003

TNKS1BP1

NO

6.63

1.00

1.80 × 10−7

0.80

0.003

RPN1

NO

4.95

0.92

7.30 × 10−7

0.36

0.081

AKIRIN1

NO

6.47

0.98

9.90 × 10−11

1.00

1.40 × 10−4

TMEM121B

NO

4.97

0.93

6.80 × 10−7

1.00

0.002

NHLRC1

NO

−9.68

1.00

3.70 × 10−22

0.98

0.013

TMX2

YES

5.48

0.68

2.60 × 10−4

0.30

0.026

KRT8P12

NO

−7.04

0.51

1.90 × 10−12

0.96

5.92 × 10−4

ENSG00000260329

NO

5.79

1.00

7.10 × 10−9

0.99

0.004

PhenoAge

CYP2J2

NO

7.13

1.00

9.80 × 10−13

0.97

0.002

TPMT

NO

−6.74

1.00

6.80 × 10−7

0.007

0.002

PURB

NO

6.29

1.00

3.10 × 10−10

0.96

0.014

KDM1B

NO

5.86

0.99

2.40 × 10−4

0.01

0.019

NHLRC1

NO

−6.03

1.00

1.60 × 10−9

0.98

0.013

Multivariate longevity

DBNDD1

NO

5.66

1.00

1.50 × 10−8

1.00

0.009

TOMM40

NO

10.47

1.00

1.20 × 10−25

0.20

0.004

CDKN2B

NO

7.28

1.00

3.40 × 10−13

0.88

0.002

FGD6

NO

5.77

1.00

8.20 × 10−9

0.99

4.37 × 10−4

FES

NO

−5.91

1.00

3.40 × 10−9

0.98

4.51 × 10−4

ENSG00000255710

NO

5.19

0.98

2.20 × 10−7

0.95

0.019

PHETA1

NO

−5.50

1.00

3.70 × 10−8

0.078

0.009

  1. High confidence results from TWAS analyses of five aging phenotypes. TWASs were conducted using cross-tissue expression weights generated from the GTEx v8 release using sparse canonical correlation analysis (sCCA). Significance was defined using a Bonferroni threshold of P < 1.32 × 10−6 (0.05/37,917 cross-tissue sCCA features). Significant TWAS associations were deemed high confidence if they passed a conditional test (joint P value < 0.05) and FOCUS fine-mapping (PIP > 0.5). Colocalization and permutation analyses were used to further assess the robustness of TWAS findings. A gene was defined as novel if it was located greater than 500 kilobases from a lead variant in the source GWAS. Statistical analyses were conducted using two-sided t-tests.
  2. TWAS transcriptome-wide association study, PIP posterior inclusion probability, FOCUS Fine-mapping Of CaUsal gene Sets, PP.H4 posterior probability that two traits are associated with a single causal variant, IEAA intrinsic epigenetic age acceleration, GTEx v8 Genotype-Tissue Expression Project version 8, GWAS genome-wide association study.
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