Table 2 |.
Identified SNP-metabolite associations, whether they have been previously reported, and potential contributors to identification
| Distinct variant-metabolite association | Index SNP | Associated metabolite | Novel association? | Novel metabolite? | Metabolite negatively associated with GFR? | Metabolite-SNP association stronger with lower GFR? | Coded allele frequency at least 50% higher in AASK than in the European population? |
|---|---|---|---|---|---|---|---|
| 1a | rs4507958 | 10-Undecenoate (11:1n1) | No (Long et al.,17 Shin et al.,18 Suhre et al.19) | No (Long et al.,17 Shin et al.,18 Suhre et al.19) | No | No | Yes |
| 2a | rs324418 | N-Palmitoylglycine | No (Long et al.17) | No (Long et al.17) | No | No | No |
| 3 | rs79319225 | 3-Methyladipate | Yes | No (Long et al.17) | Yes | No | Yes |
| 4a | rs7528838 | alpha-Hydroxyisovalerate | No (Shin et al.18) | No (Yu et al.,4 Shin et al.,18 Long et al.17) | Yes | Yes (P = 0.02) | Yes |
| 5a | rs7528838 | 2-Hydroxy-3-methylvalerate | Yes | No (Long et al.17) | Yes | Yes (P = 0.006) | Yes |
| 6a | rs7587577 | N-Acetylasparagine | No (Long et al.17) | No (Long et al.17) | Yes | No | Yes |
| 7a | rs7587577 | N-Acetyl-3-methylhistidine | No (Long et al.17) | No (Long et al.17) | Yes | No | Yes |
| 8a | rs11126412 | N-Acetyl-1-methylhistidine | No (Long et al.17) | No (Long et al.17) | Yes | No | Yes |
| 9a | rs11126412 | N-Acetylphenylalanine | No (Long et al.17) | No (Yu et al.,4 Long et al.17) | Yes | No | Yes |
| 10a | rs13431529 | N2-Acetyllysine | Yes | Yes | Yes | No | Yes |
| 11a | rs13409366 | N-Acetylcitrulline | No (Long et al.17) | No (Long et al.17) | Yes | No | Yes |
| 12a | rs13409366 | N-Acetylglutamine | No (Long et al.17) | No (Long et al.17) | Yes | No | Yes |
| 13 | rs13409366 | N-Acetylkynurenine | Yes | Yes | Yes | No | Yes |
| 14a | rs6546854 | N-Acetylleucine | Yes | Yes | Yes | No | Yes |
| 15a | rs10168931 | N-Acetylarginine | Yes | Yes | Yes | No | Yes |
| 16a | rs10206899 | N-delta-Acetylornithine | No (Long et al.17) | No (Suhre et al.,19 Yu et al.,4 Shin et al.,18 Long et al.,17 Li et al.20) | Yes | No | Yes |
| 17 | rs951389793 | Cysteinylglycine | Yes | No (Long et al.17) | No | Yes (P = 0.007) | Yes |
| 18a | rs1976391 | Biliverdin | No (Long et al.17, Yu et al.,4 Shin et al.18) | No (Long et al.,17 Yu et al.,4 Shin et al.18) | No | No | No |
| 19a | rs4148325 | Bilirubin (E,E) | No (Long et al.17, Yu et al.,4 Hong et al.,21 Krumsiek et al.,22 Suhre et al.19) | No (Yu et al.,4 Shin et al.,18 Long et al.,17 Hong et al.,21 Krumsiek et al.,22 Suhre et al.19) | No | No | Yes |
| 20 | rs62184450 | Cysteinylglycine | Yes | No (Long et al.17) | No | Yes (P = 0.04) | Yes |
| 21a | rs73835707 | N-Acetylmethionine | Yes | No (Long et al.17) | Yes | No | Yes |
| 22 | rs73835707 | N-Acetylmethionine sulfoxide | Yes | Yes | Yes | No | Yes |
| 23a | rs2229152 | N-Acetylalanine | No (Yu et al.32) | No (Yu et al.,4 Shin et al.,18 Yu et al.,32 Long et al.17) | Yes | No | Yes |
| 24 | rs1973612 | Histidylalanine | Yes | Yes | No | No | No |
| 25a | rs344514 | 3-Aminoisobutyrate | No (Rhee et al.,23 Long et al.17) | No (Rhee et al.,23 Long et al.17) | Yes | No | Yes |
| 26 | rs60132035 | Sphingomyelin (d18:1/20:1, d18:2/20:0) | Yes | No (Long et al.17) | No | No | Yes |
| 27a | rs7780766 | N-Acetylhistidine | No (Long et al.17) | No (Long et al.17) | Yes | No | Yes |
| 28 | rs139981949 | Glycohyocholate | Yes | Yes | No | No | Yes |
| 29 | rs76541360 | 1-Arachidonoyl-GPI (20:4) | Yes | No (Long et al.17) | No | No | Yes |
| 30a | rs59095288 | 6-Oxopiperidine-2-carboxylate | Yes | Yes | Yes, weak | No | Yes |
| 31a | rs55758160 | 2′-O-Methyluridine | No (Yousri et al.33) | No (Yousri et al.33) | No | No | No |
| 32a | rs57294583 | 2′-O-Methylcytidine | Yes | Yes | No | No | No |
| 33a | rs142514677 | N-Acetyl-aspartyl-glutamate | Yes | Yes | Yes, weak | No | Yes |
| 34 | rs150556827 | N-Acetyl-aspartyl-giutamate | Yes | Yes | Yes, weak | No | Yes |
| 35a | rs174564 | 1-Arachidonoyl-GPC (20:4n6) | No (Long et al.17) | No (Yet et al.,24 Long et al.17) | No | No | No |
| 36a | rs115780269 | N-Acetyltryptophan | Yes | Yes | Yes | No | Yes |
| 37 | rs115780269 | N-Acetylkynurenine | Yes | Yes | Yes | No | Yes |
| 38a | rs115780269 | N-Acetyltyrosine | Yes | No (Long et al.17) | Yes | No | Yes |
| 39a | rs115780269 | N-Acetylphenylalanine | No (Long et al.17) | No (Yu et al.,4 Long et al.17) | Yes | No | Yes |
| 40a | rs114419265 | Glycochenodeoxycholate glucuronide | No (Hong et al.21) | No (Hong et al.21) | No | No | Yes |
| 41a | rs34708625 | Ethylmalonate | No (Long et al.17) | No (Long et al.17) | Yes | No | No |
| 42a | rs114080902 | N-Formylanthranilic acid | Yes | Yes | Yes | No | Yes |
AASK, African American Study of Kidney Disease and Hypertension; GFR, glomerular filtration rate; SNP, single-nucleotide polymorphism.
Higher confidence of findings given previous literature or subsequent replication.
Details on the comparison of allele frequencies between AASK participants and the general population can be found in Supplementary Table S3. Details about the novelty of associations/metabolites can be found in Supplementary Table S4.