Table 2 Summary of the GWAS analysis of the MDD-related clusters in the UKB cohort (N = 249,167)

From: Unique genetic and risk-factor profiles in clusters of major depressive disorder-related multimorbidity trajectories

 

Cluster 1

Cluster 2

Cluster 3

Cluster 4

Cluster 5

Cluster 6

Cluster 7

N per SNP

246,639–249,167

λ

1.2168

1.1523

1.0772

1.0864

1.0833

1.1843

1.1555

h2

0.0483

0.0331

0.0171

0.0186

0.0148

0.037

0.0385

SNPs

6,266,283

Significant SNPsa

1908

1952

1451

1924

1

52

5986

Significant locia

15

18

14

13

1

3

36

Significant genesb

87

62

51

110

5

15

271

Significant gene setsc

62

67

72

87

3

0

129

Significant MDD- associated genesd

HLA-DQA1, HLA-DQB1, LIN28B, LST1, HLA-B

HLA-DQA1, HLA-DQB1, ITPR3, HLA-B

HLA-DQA1, HLA-DQB1, HLA-B

HLA-DQA1, HLA-DQB1, HLA-B, PSORS1C1, PSORS1C2

LST1

PSORS1C1, PSORS1C2

HLA-DQA1, HLA-DQB1, HLA-B, HSPA1A, HSPE1-MOB4, LST1, MOB4, PLCL1, PSORS1C1, PSORS1C2, RFTN2, SLC44A4, SPPL3, SF3B1, TRAF3

Enrichment of MDD-associated genesd within cluster-specific genes

P-valueHGT = 0.037

P-valueGSEA < 10-16

P-valueHGT = 0.047

P-valueGSEA = 5.44 × 10-7

P-valueHGT = 0.064

P-valueGSEA = 6.55 × 10-7

P-valueHGT = 0.064

P-valueGSEA = 1.56 × 10-10

P-valueHGT = 0.065

P-valueGSEA = 3.79 × 10-5

P-valueHGT = 0.064

P-valueGSEA  < 10-16

P-valueHGT = 2.77e-05

P-valueGSEA = 6.55 × 10-7

  1. λ: genomic inflation factor based on LD score regression; h2: genetic heritability.
  2. Association analyses were performed for each cluster using linear regression to test the association between each SNP and the posterior log odds of cluster membership, controlling for age, sex, the first ten genetic principal components, and the genotyping array. The significance of the over-enrichment of MDD-associated genes (according to Howard et al. 5) within the cluster-associated genes was assessed by conducting one-sided hypergeometric tests and Gene Set Enrichment Analysis (GSEA). To account for multiple comparisons, we applied Holm’s correction method.
  3. GSEA Gene Set Enrichment Analysis, HGT Hypergeometric test.
  4. aThe significance of SNPs refers to a genome-wide significance level of 5 × 10-8.
  5. bResults from MAGMA gene-level analyses, significance based on Holm correction, using 19,843 protein-coding genes.
  6. cResults from the g:Profiler method, significance based on the g:SCS correction algorithm at a significance threshold of 0.01.
  7. dOverlapping significant MDD-associated genes according to the GWAS meta-analysis by Howard et al. 5 of a total of 269 genes.
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