An atlas of genetic influences on human blood metabolites

Shin et al., Nature Genetics, 2014 [ Article | SI Text ]

Locus 43: SLC22A4|SLC22A5 (5q31.1)

Meta-analysis summary statistics for associations meeting genome-wide significance
Lead SNPBiochemicalsEA/OANtotalEAFEffect (SE)PmetaDetails
rs272889 valine / isovalerylcarnitine A/G 7330 0.37 -0.039 (0.003) 2.56·10-51 show
rs11950562 isovalerylcarnitine A/C 7344 0.52 0.036 (0.003) 2.31·10-41 show
rs273913 3-dehydrocarnitine* T/C 7361 0.38 0.026 (0.003) 1.08·10-25 show
rs419291 carnitine T/C 7349 0.37 0.008 (0.001) 3.1·10-18 show
rs7727544 propionylcarnitine T/C 7364 0.56 -0.015 (0.002) 6.61·10-16 show
rs274567 acetylcarnitine T/C 7356 0.37 0.018 (0.003) 2.85·10-12 show
rs272869 hexanoylcarnitine A/G 7340 0.37 0.022 (0.003) 1.4·10-11 show
rs273914 oleoylcarnitine A/T 7263 0.37 0.023 (0.004) 3.04·10-11 show
rs11950562 homostachydrine* A/C 2891 0.53 0.030 (0.005) 6.75·10-11 show

EA = effect allele; OA = other allele; EAF = frequency of effect allele;

Summary of biological annotations
SNPrs272889
Chromosomal locationChr5: 131,693,277 (5q31.1)
Gene (distance)SLC22A4 (0)
Predicted causal geneSLC22A5
Gene/protein classification-
Metabolite (Pathway)valine (Valine, leucine and isoleucine metabolism; Amino acid)
isovalerylcarnitine (Valine, leucine and isoleucine metabolism; Amino acid)
Biochemical locus-metabolite relationshipSLC22A4 and SLC22A5 encode the OCTN1 and OCTN2 organic cation transporters and both have documented carnitine transport activity [21045919]. Ratio interpretation: isovalerylcarnitine is related to isovaleryl-CoA, an intermediate in the breakdown of branch chain amino acid, leucine. Valine, as an additional branch chain amino acid, may be normalizing for the branch chain amino acid pool ('normalizing').
eQTL associationsSLC22A4 (S), P4HA2 (L), P4HA2 (S), PDLIM4 (S), RAD50 (F), RAD50 (L), SLC22A5 (L), SLC22A5 (S)

F = adipose tissue; S = skin cells; L = lymphoblastoid cells; H = liver cells;

Medical information
Complex trait associationsHeight [20881960]
Known metabolite associationsisovalerylcarnitine [21886157]; Valine/C5 [20037589]
Inborn error of metabolismCarnitine brain transporter deficiency

Pharmacological information
ChEMBL IDtransporter, transporter
Drug information CHEMBL2073668/CHEMBL2073693

Locus information for top associated metabolite

HapMap2 imputation

Imputation HapMap

1KGP imputation

Imputation 1KGP

 

Network view
Association map