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. 2018 Apr 3;12:1–11. doi: 10.1016/j.molmet.2018.03.015

Table 1.

Associations of GWAS and GWAMA derived human metabolism SNPs in GWAMA data for mental disorders and other mental/behavioral phenotypes.

SNP Region Mapped Gene Effect allele MetaboliteA p-value for metabolite or metabolite ratio Exponents of p-values per mental phenotype
 Effect directionsB Source
BMI Ed_Att Neuroticism Alzheimer Schizophrenia Well-being Aggression Anxiety Depression MDD Bipolar Autism Internalizing ADHD
rs2802729 1q43 SDCCAG8 A eGFRcrea 2.0E-8 −3 −6* −2 −3 −2 A: metab↓; Schizo↓ [31]
rs6546838 2p13.1 ALMS1 A eGFRcrea 8.0E-20 −3 −6* A: metab ↓; Schizo↓ [31]
rs9309473 2p13.1 ALMS1 G N-acetylated compound(s) 4.1E-19 −3 −6* G: metab↑; Schizo↑ [46]
rs11884776 2p13.1 ALMS1 C N-acetylated compounds 6.0E-17 −3 −6* C: metab↑; Schizo↓ [45]
rs10469966 2p13.1 ALMS1 A X-12093 1.0E-51 −4 −7* A: metab↑; Schizo↑ [13]
rs6546847 2p13.1 ALMS1 A N-acetylated compounds 5.3E-161 −3 −6* A: metab↑; Schizo↓ [45]
rs13391552 2p13.1 ALMS1 A N-acetylornithine 5.0E-252 −3 −6* A: metab↓; Schizo↑ [63]
rs6546857 2p13.1 ALMS1 - NAT8 A (X-11787) 1.0E-23 −3 −7* A: metab↑; Schizo↓ [64]
rs10178409 2p13.1 ALMS1 - NAT8 T N-acetylaspartate 1.0E-95 −3 −5 T: metab↑; Schizo↑ [65]
rs13538 2p13.1 NAT8 A N-acetylornithine/myo-inositol 8.0E-157 −3 −5 A: metab↑; Schizo↓ [13]
rs13538 2p13.1 NAT8 G eGFRcrea 5.0E-14 −3 −5 G: metab↑; Schizo↑ [66]
rs13538 2p13.1 NAT8 A X-11787 2.0E-23 −3 −5 A: metab↑; Schizo↓ [64]
rs10206899 2p13.1 ALMS1P T N-acetylornithine 2.0E-14 −3 −5 T: metab↑; Schizo↓ [13]
rs1260326 2p23.3 GCKR A HDL total 6.3E-36 −5 −3 −3 A: metab↑;BMI↓ [67]
rs1260326 2p23.3 GCKR n.a. S-HDL-P 1.0E-12 −5 −3 −3 ? [68]
rs1260326 2p23.3 GCKR C mannose 6.0E-56 −5 −3 −3 C: metab↑; BMI↑ [69]
rs1260326 2p23.3 GCKR T eGFRcrea 3.0E-14 −5 −3 −3 T: metab↑; BMI↓ [66]
rs1260326 2p23.3 GCKR T glucose/mannose 3.0E-148 −5 −3 −3 T: metab↑; BMI↓ [13]
rs7570971 2q21.3 RAB3GAP1 A 1.5-anhydroglucitol 8.0E-45 −6* −2 A: metab↓; BMI ↓ [13]
rs1047891 2q34 CPS1 A plasma homocysteine levels 9.0E-13 −5 A: metab↑; BMI↑ [70]
rs715 2q34 CPS1 T serine 3.0E-11 −6 T: metab↓; BMI↓ [71]
rs715 2q34 CPS1 T glycine 3.0E-50 −6 T: metab↓; BMI↓ [13],[72],[65]
rs10513801 3q27.2 ETV5 T eGFRcrea 1.0E-9 −21* −5 T: metab↑; BMI↑; EdAtt↑ [31]
rs12654264 5q13.3 HMGCR T LDLc 1.0E-20 −8* −3 −2 −2 T: metab ↓; BMI↓ [58]
rs7759001 6p22.1 ZNF204P A eGFRcrea 2.0E-8 −2 −5 −2 −3 A: metab↓; Schizo↓ [31]
rs2762353 6p22.2 SLC17A1 A 4-androsten-3beta,17beta-diol disulfate 2 3.0E-13 −5 −3 A; metab↑; Schizo↑ [13]
rs9400467 6q21 SLC16A10 T tyrosine 7.0E-14 −6* T: metab ↓; Schizo↓ [13],[71]
rs4841132 8p23.1 LOC157273 n.a. free cholesterol in medium HDL 2.0E-9 −3 −5 n.a. [68]
rs15676 9q34.11 TBC1D13 A indolelactate 1.0E-12 −3 −5 −2 A: metab↑; Schizo↑ [13]
rs9527 10q24.32 C10orf32 C10orf32-ASMT A dimethylarsinic acid in urine 3.0E-9 −2 −5 n.a. [43]
rs1278587 11q13.4 NADSYN1 T vitamin D insufficiency 2.0E-27 −5 n.a. [73]
rs3184504 12q24.12 SH2B3 T kynurenine 6.0E-18 −6 T: metab↑; BMI↓ [13]
rs2066938 12q24.31 UNC119B A butyrylcarnitine 3.1E-630 −6* −4 A: metab↓; EdAtt↑ [13]
rs2066938 12q24.31 UNC119B A butyrylcarnitine /propionylcarnitine 4.4E-305 −6* −4 A: metab↓; EdAtt↑ [63]
rs2014355 12q24.31 ACADS T C3/C4 5.0E-96 −6* −3 T: metab↓; edAtt↑ [12]
rs3916 12q24.31 ACADS G unknown 2.4E-22 −6* −3 n.a. [45]
rs4144027 14q32.33 LOC105370690 T aspargine 1.0E-11 −2 −5 −2 −2 −2 T: metab↑; Schizo↓ [13]
rs12446492 16p12.3 PDILT A uromodulin indexed to creatinine 6.0E-27 −5 A: metab↓; BMI↑ [74]
rs7200543 16p13.11 PDXDC1 A PC aa C38:3 (Glycerophospholipid levels) 3.0E-17 −5 −3 −2 A: metab↑; BMI↑ [71]
rs7200543 16p13.11 PDXDC1 G 1-eicosatrienoylglycero-phosphocholine /1-linoleoylglycero-phosphocholine 5.0E-16 G: metab↓; BMI↓ [63]
rs11075253 16p13.11 PDXDC1, NTAN1 A linoleic acid/PUFA 5.0E-15 −5 −2 −2 −2 A: metab↓; EdAtt↑ [75]
rs8056893 16q22.1 SLC7A6 A glutaroyl carnitine 2.0E-30 −5 −2 −2 A: metab↓; BMI↓ [13]
rs2863979 16q22.1 SLC7A6 A lysine 1.0E-17 −5 −2 −2 −2 A: metab↑; BMI↓ [13]
rs9916302 17q12 FBXL20 T eGFRcrea 5.0E-15 −5 −3 T: metab↓; EdAtt↑ [31]
rs7219014 17q12 CDK12 A histidine/τ-methylhistidine 4.0E-26 −5 −3 A: metab↓; EdAtt↓ [65]
rs4808136 19p13.11 ELL A myo-inositol 5.0E-14 −3 −5 −2 −3 −2 A: metab↑; Alz↑ [13]
rs4803750 19q13.32 BCL3 G LDL-C assay fasting 1.0E-27 −13* G: metab↓; Alz↓ [67]
rs7412 19q13.32 APOE T L-LDL-FC 3.0E-58 −2 −22* T: metab↓; Alz ↓ [75]
rs4420638 19q13.32 APOC1- APOC1P1 A LDL-C 1.0E-14 −4 −454* −2 G: metab↑; Alz↑ proxy [76]
rs2287921 19q13.33 RASIP1 C FUT2 - fucose 7.0E-19 −2 −2 −2 −3 −6* C: metab↑, BIP↑ [45]

Horizontal lines separate chromosomal regions of 1 Mb.

Bold values indicate significant results upon correction for 516 SNPs (p < 9.7 × 10-5).

*Significant values upon correction for 14 traits and 516 SNPs (p < 6.92 × 10-6).

ADHD: Attention Deficit/Hyperactivity Disorder; Aggression: Aggressive behavior; Alz: Alzheimer's disease; Autism: Autism spectrum disorder; Bipolar: Bipolar disorder; BMI: Body mass index; Ed_Att: Educational attainment; Internalizing: Internalizing problems; GWAS: Genome-wide association study; GWAMA: Genome-wide association meta-analysis; MDD: Major depressive disorder, metab: Metabolite or ratio of metabolites.

A

Metabolite, ratio of metabolites, or metabolism markers with lowest p-value in GWAMA.

B

Upward arrows indicate positive beta-values or odds ratios >1, downward arrows negative beta-values or odds ratios <1 for the phenotype showing the lowest p-value.