Table 2 Genetic variants associated with cardiometabolic disease-related (dh)ceramides.

From: Dihydroceramide- and ceramide-profiling provides insights into human cardiometabolic disease etiology

   

EPIC-Potsdam

(n = 1094)

EUROSPAN

(n = 4034)

FHSOCa

(n = 2217)

Chr

Rsid

Nearest gene

beta (SE)

P

beta (SE)

P

beta (SE)

P

Cer20:0

 22

rs7290187

GRAMD4

−0.186 (0.041)

5.3E–06

0.003 (0.001)

0.011

NA

NA

Cer22:0

 20

rs686548

SPTLC3

−0.203 (0.039)

2.1E-07

NA

NA

−0.031 (0.005)

6.8E-11

 20

rs680379

SPTLC3

−0.201 (0.039)

2.3E-07

0.054 (0.007)

1.3E-13

−0.031 (0.005)

4.0E-11

 20

rs1321940

SPTLC3

−0.201 (0.039)

2.4E-07

NA

NA

−0.031 (0.005)

3.5E-11

 20

rs168622

SPTLC3

−0.197 (0.039)

4.1E-07

0.054 (0.007)

1.2E-13

−0.031 (0.005)

3.0E-11

 20

rs2327451

SPTLC3

−0.199 (0.040)

8.4E-07

−0.054 (0.008)

1.4E-12

−0.029 (0.005)

5.7E-09

 20

rs2327452

SPTLC3

−0.191 (0.040)

2.5E-06

NA

NA

−0.029 (0.005)

5.6E-09

 20

rs364585

SPTLC3

−0.197 (0.039)

4.2E-07

0.054 (0.007)

1.1E-13

−0.031 (0.005)

3.1E-11

 20

rs3843765

SPTLC3

−0.197 (0.040)

1.1E-06

NA

NA

−0.029 (0.005)

5.7E-09

 20

rs3848744

SPTLC3

−0.190 (0.040)

3.1E-06

NA

NA

−0.029 (0.005)

4.6E-09

 20

rs3848745

SPTLC3

−0.199 (0.040)

8.4E-07

NA

NA

−0.029 (0.005)

4.7E-09

 20

rs3848746

SPTLC3

−0.190 (0.040)

2.4E-06

NA

NA

−0.029 (0.005)

5.5E-09

 20

rs3903703

SPTLC3

−0.198 (0.040)

8.7E-07

0.054 (0.008)

1.4E-12

−0.029 (0.005)

4.8E-09

 20

rs438568

SPTLC3

−0.190 (0.039)

1.2E-06

NA

NA

−0.031 (0.005)

3.5E-11

 20

rs4508668

SPTLC3

−0.199 (0.040)

8.2E-07

0.054 (0.008)

1.4E-12

−0.028 (0.005)

6.0E-09

 20

rs4814173

SPTLC3

−0.198 (0.040)

9.4E-07

NA

NA

−0.029 (0.005)

5.0E-09

 20

rs4814175

SPTLC3

−0.200 (0.039)

3.2E-07

NA

NA

−0.031 (0.005)

2.8E-11

 20

rs4814176

SPTLC3

−0.200 (0.039)

3.2E-07

0.054 (0.007)

1.0E-13

−0.031 (0.005)

3.6E-11

 20

rs6041735

SPTLC3

−0.187 (0.041)

4.6E-06

NA

NA

 − 0.029 (0.005)

5.1E-09

 2

rs780094

GCKR

−0.193 (0.040)

1.6E-06

0.016 (0.007)

0.022

NA

NA

 2

rs780093

GCKR

−0.188 (0.040)

2.9E-06

0.016 (0.007)

0.022

NA

NA

  1. Shown are all associations of SNPs with disease-related (dh)ceramides that were genome-wide suggestively significant (10−5) in EPIC-Potsdam and available for replication in EUROSPAN or FHSOC or both. Note that the associations of the SNP associated with Cer20:0 and the two Cer22:0-associated SNPs in the GCKR-gene with Cer22:0 were not significant after multiple testing correction (FDR > 0.05); all replication of Cer22:0-associated SNPs in the SPTLC3 gene region were significant after multiple testing correction (FDR < 0.05) (corrected for the number of SNPs available for replication).
  2. EPIC-Potsdam: 1094 participants, GWAS adjusted for age and sex, ceramides log-transformed, and variance standardized. EUROSPAN37: 4034 participants, GWAS adjusted for age and sex, ceramides log-transformed, and variance standardized. FHSOC39: 2217 participants, GWAS adjusted for kinship, age, sex, diabetes, smoking status, systolic blood pressure, antihypertensive treatment, body mass index (BMI), and two associated principal components (PC1, PC9) of population stratification. Estimates were reported per standard deviation (EPIC-Potsdam, EUROSPAN) and per µM (FHSOC).
  3. aThe beta estimates from FHSOC included in the MR were extracted from Table 2 in the publication ‘Genetic Architecture of Circulating Very-Long-Chain (C24:0 and C22:0) Ceramide Concentrations’ by Cresci et al.39.
  4. ITPR1 inositol 1,4,5-trisphosphate receptor type 1 (encoding a plasma membrane receptor), GRAMD4 GRAM domain containing 4 (innate immune response), SPTLC3 Serine Palmitoyltransferase Long Chain Base Subunit 3 (encoding the key enzyme in sphingolipid biosynthesis), GCKR Glucokinase Regulator (encoding the glucokinase regulator protein), PM plasma membrane SL sphingolipid, FHSOC Framingham Heart Study Offspring Cohort.
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