rs11158503 (SGPP1): Blood Lipid Metabolites

Key takeaways

• rs11158503 is associated with blood lipid metabolite levels in both South Asian and British populations, based on a lipidomics study of over 19,000 participants.
• The variant maps to the SGPP1 locus, flagged among novel loci with cardiometabolic disease-relevant lipid associations.
• The ALT allele reduces SGPP1 gene expression in thyroid tissue and ESR2 (estrogen receptor 2) expression in whole blood, per GTEx data.
• The ALT allele increases expression of a nearby transcript (ENSG00000274015) in tibial nerve, subcutaneous adipose tissue, and heart left ventricle.
• Evidence is from a single discovery study; specific per-variant effect sizes for rs11158503 were not reported in the available study text.

What the research says A genome-wide lipidomics study in 5,662 South Asian hospital controls from Pakistan and 13,814 healthy British blood donors used direct infusion high-resolution mass spectrometry (DIHRMS) - a technique measuring hundreds of individual lipid species in blood serum simultaneously - to map genetic influences on the human blood lipidome. The study identified 253 genotype-lipid associations at 24 independent loci in the South Asian cohort and 502 lipid QTLs (quantitative trait loci, genetic positions where variants predict a measurable biological trait) at 38 independent loci in the British cohort, with the SGPP1 locus listed among novel findings relevant to cardiometabolic disease. Separately, GTEx expression data shows the ALT allele at this position reduces SGPP1 expression in thyroid tissue and reduces ESR2 expression in whole blood GTEx Portal.

Reported associations

• Blood lipid metabolites (South Asian population): Novel lipid associations identified at the SGPP1 locus in 5,662 Pakistani controls from the PROMIS study, among 253 genotype-lipid associations across 24 independent loci.
• Blood lipid metabolites (British population): Lipid associations at the SGPP1 locus identified in 13,814 British blood donors from the INTERVAL study, among 502 lipid QTLs at 38 independent loci.
• Cardiometabolic disease relevance: The SGPP1 locus is described as a cardiometabolic disease locus, with novel lipid metabolite associations providing new biological insights into lipid regulation.

Evidence quality The primary evidence comes from a single lipidomics discovery study conducted in two ancestrally distinct cohorts totaling approximately 19,476 participants. Both the Pakistan cohort (PROMIS) and the UK cohort (INTERVAL) used the same DIHRMS lipidomics platform, enabling cross-population comparison of genetic effects on circulating lipids. However, the available study text does not report specific p-values, effect sizes, or the names of individual lipid species linked to rs11158503 at this locus - only that SGPP1 is among loci with novel cardiometabolic-relevant associations. No independent replication cohorts for this specific locus finding are described in the available source material, and the evidence should be treated as preliminary. The GTEx eQTL associations are FDR-significant from 953 donors in GTEx v11, but eQTL effects describe gene regulation mechanisms and are not direct measures of disease risk.

Tissue-specific expression effects

• ENSG00000274015 (a transcript located near this locus): The ALT allele is linked to increased expression in tibial nerve, subcutaneous adipose tissue, and left ventricle of the heart GTEx Portal.
• ESR2 (estrogen receptor 2): The ALT allele is linked to reduced expression in whole blood GTEx Portal.
• WDR89: The ALT allele is linked to reduced expression in EBV-transformed lymphocytes and esophageal mucosa GTEx Portal.
• SGPP1: The ALT allele is linked to reduced expression in thyroid tissue GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.