Table 1.
Exome chip variants associated with metabolite traits at suggestive significance in EPIC-Potsdam and replication in KORA F4.
| Metabolite trait | Chr | SNPb (Locus) | EPIC-Potsdam a | KORA F4 | pooled | Replicated e | Consequence (GRCH37) | scaled CADD score | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| nc | allele frequency (coded allele) | Beta (SE)d | p | nc | allele frequency (coded allele) | Beta (SE)d | p | Beta (SE) d | p | ||||||
| PC aa C42:1/ PC aa C42:0 | 1 | rs41282492 (CHIA) | 2190 | 87.9 (A) | 0.25 (0.05) | 1.01 E-07 | 2692 | 87.8 (A) | −0.09 (0.04) | 2.78 E-02 | 0.08 (0.17) | 6.41 E-01 | Asn45Asp | 0.01 | |
| Tyrosine/ Methionine | 6 | rs3204953 (REV3L) | 2201 | 85.2 (C) | −0.28 (0.04) | 9.80 E-12 | 2689 | 84.0 (C) | −0.20 (0.03) | 1.49 E-09 | −0.24 (0.04) | 7.45 E-09 | * | Val3064Ile | 32 |
| PC aa C36:1/ PC aa C34:1 | 10 | rs10885997 (PNLIPRP2) | 2201 | 58.8 (A) | −0.17 (0.03) | 5.54 E-08 | 2692 | 58.6 (A) | −0.09 (0.02) | 1.70 E-05 | −0.13 (0.04) | 1.46 E-03 | * | Synonymous variant | 7.74 |
| PC aa C40:5/ PC aa C38:5 | 11 | rs499974 (MOGAT2) | 2203 | 81.2 (C) | −0.21 (0.04) | 2.25 E-08 | 2692 | 81.3 (C) | −0.18 (0.03) | 6.97 E-08 | −0.19 (0.03) | 6.88 E-15 | * | downstream gene variant | 8.66 |
| PC ae C44:6/ PC aa C42:1 | 11 | rs10790162 (BUD13) | 2203 | 6.70 (A) | −0.32 (0.06) | 1.57 E-07 | 2691 | 7.56 (A) | −0.06 (0.05) | 2.51 E-01 | −0.19 (0.13) | 1.53 E-01 | intron variant | 6.55 | |
| SM C16:1/ PC aa C28:1 | 14 | rs7157785 (SGPP1) | 2203 | 83.6 (G) | 0.49 (0.04) | 1.45 E-35 | 2691 | 82.6 (G) | 0.40 (0.03) | 2.27 E-40 | 0.45 (0.04) | 2.39 E-24 | * | regulatory region variant | 1.91 |
| SM (OH) C22:2/ SM C24:0 | 14 | rs7157785 (SGPP1) | 2203 | 83.6 (G) | −0.22 (0.04) | 5.46 E-10 | 2692 | 82.6 (G) | −0.24 (0.03) | 6.40 E-15 | −0.23 (0.02) | 9.22 E-24 | * | regulatory region variant | 1.91 |
| SM (OH) C22:2/ SM (OH) C14:1 | 14 | rs7157785 (SGPP1) | 2202 | 83.6 (G) | 0.42 (0.04) | 2.79 E-27 | 2692 | 82.6 (G) | 0.37 (0.03) | 4.21 E-28 | 0.40 (0.03) | 7.09 E-55 | * | regulatory region variant | 1.91 |
| SM (OH) C22:2/ SM (OH) C22:1 | 14 | rs7157785 (SGPP1) | 2202 | 83.6 (G) | −0.30 (0.04) | 6.00 E-15 | 2691 | 82.6 (G) | −0.27 (0.03) | 9.89 E-17 | −0.28 (0.02) | 7.52 E-31 | * | regulatory region variant | 1.91 |
| 19 | rs7412 (APOE) | 2202 | 91.4 (C) | −0.27 (0.05) | 1.30 E-07 | 2688 | 91.5 (C) | −0.14 (0.04) | 1.76 E-03 | −0.20 (0.06) | 1.48 E-03 | * | Arg202Cys | 30 | |
| PC aa C36:3/ PC aa C34:3 | 16 | rs1136001 (NTAN1) | 2201 | 67.0 (G) | 0.18 (0.03) | 5.58 E-09 | 2690 | 69.0 (G) | 0.14 (0.03) | 3.29 E-07 | 0.16 (0.02) | 1.18 E-14 | * | His283Asn | 0.81 |
Chr, chromosome; SE, standard error; CADD, Combined Annotation Dependent Depletion. aonly sub-cohort; bgene variants are reported on the forward strand of NCBI build 37; cmetabolite outliers (±4SD) were excluded; dmetabolites (µmol/L) were ln-transformed and standardized, effect estimates are adjusted for age and sex; esignificance threshold: 0.05/11 tests = 4.55 × 10−3.