Table 1 Top enriched biological pathways in complex traits

From: Large-scale genome-wide enrichment analyses identify new trait-associated genes and pathways across 31 human phenotypes

Phenotype

Top enriched pathway

Database

# of signals (genes)

log10BF

Neurological traits

Depressive symptoms

Eicosapentaenoate biosynthesis

HumanCyc (PC)

2 (12)

36.9

Alzheimer’s disease

Golgi associated vesicle biogenesis

Reactome (PC)

3 (49)

83.7

Anthropometric traits

Adult height

Endochondral ossification

WikiPathways (BS)

57 (65)

68.9

Immune-related traits

Crohn’s disease

Inflammatory bowel disease

KEGG (BS)

24 (61)

25.6

Inflammatory bowel disease

Inflammatory bowel disease

KEGG (BS)

26 (61)

24.2

Rheumatoid arthritis

NFAT-dependent transcriptiona

PID (BS)

11 (45)

10.0

Ulcerative colitis

Inflammatory bowel disease

KEGG (BS)

16 (61)

11.8

Metabolic traits

Age at natural menopause

IL-2Rβ in T-cell activation

BioCarta

2 (37)

866.7

Coronary artery disease

p75(NTR)-mediated signaling

PID (BS)

4 (55)

16.0

Fasting glucose

Hexose transport

Reactome (BS)

4 (47)

1,898.4

Gout

Osteoblast signaling

WikiPathways (BS)

2 (13)

30.6

High-density lipoprotein

Statin pathway

WikiPathways (BS)

18 (30)

113.9

Low-density lipoprotein

Chylomicron-mediated lipid transport

Reactome (PC)

11 (17)

65.5

Myocardial infarction

Glutathione synthesis and recycling

Reactome (PC)

2 (11)

9.6

Total cholesterol

Glucose transport

Reactome (BS)

2 (41)

833.2

Triglycerides

Targets of C-MYC activationb

PID (BS)

3 (79)

604.9

Serum urate

Transport of glucose and othersc

Reactome (PC)

4 (95)

1,558.1

Hematopoietic traits

Hemoglobin (HB)

RNA polymerase I transcription

Reactome (BS)

27 (107)

2,641.3

Mean cell HB (MCH)

Meiotic synapsis

Reactome (PC)

21 (72)

2,334.3

MCH concentration

SIRT1 negative regulation of rRNAd

Reactome (PC)

3 (63)

700.8

Mean cell volume

DNA methylation

Reactome (PC)

28 (61)

2,077.3

Packed cell volume

RNA polymerase I promoter opening

Reactome (PC)

27 (59)

217.5

Red blood cell count

GSL biosynthesis (neolacto series)

KEGG (PC)

2 (21)

391.2

  1. For each trait here we report the most enriched pathway (if any) that (i) has an enrichment Bayes factor (BF) greater than 108; (ii) has at least 10 and at most 200 member genes; (iii) has at least two member genes with enrichment P1 > 0.9 (denoted as “signals”); and (iv) passes the visual and likelihood ratio sanity checks (Supplementary Fig. 17). All BFs reported here are larger than corresponding BFs that SNPs within 100 kb of transcribed regions of all genes are enriched (Supplementary Fig. 19). The corresponding baseline and enrichment parameter estimates are provided in online results (Methods). P1 posterior probability that at least one SNP within 100 kb of the transcribed region of a given gene has nonzero effect on the target trait; CaN: calcineurin; NFAT: nuclear factor of activated T cells; IL-2Rβ: interleukin-2 receptor beta chain; p75(NTR): p75 neurotrophin receptor; SIRT1: Sirtuin 1; GSL: glycosphingolipid; PC: Pathway Commons63; BS: NCBI BioSystems64
  2. a The full name of this pathway is “calcineurin-regulated NFAT-dependent transcription in lymphocytes”
  3. b The full name of this pathway is “validated targets of C-MYC transcriptional activation”
  4. c The full name of this pathway is “transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds”
  5. d The full name of this pathway is “SIRT1 negatively regulates ribosomal RNA expression”
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