rs113338490 (SGPP1): Blood Lipid Metabolism Variant

Key takeaways

• rs113338490 at the SGPP1 locus was identified with novel blood lipid associations in a study of over 19,000 South Asian and British participants.
• SGPP1 is among a small group of genetic loci linked to distinctive lipid patterns at cardiometabolic disease-relevant regions.
• This variant reduces WDR89 gene activity across fat tissue, immune cells, and skin, based on gene expression data from 953 donors.
• A nearby uncharacterized gene (ENSG00000274015) shows increased activity in nerve, colon, and connective tissue cells for the same variant.
• Evidence is preliminary: one published study, no specific per-variant effect sizes available in the provided text.

What the research says A genome-wide lipidomics study combining 5,662 Pakistani adults (PROMIS cohort) and 13,814 British blood donors (INTERVAL cohort) identified novel blood lipid associations at the SGPP1 locus, placing it among a small set of cardiometabolic disease-relevant genetic regions. The study applied direct infusion high-resolution mass spectrometry (DIHRMS), a method that captures individual lipid species rather than broad lipid classes, detecting 253 lipid quantitative trait loci (QTLs - genetic variants that influence circulating lipid levels) across 24 independent loci in PROMIS and 502 QTLs at 38 independent loci in INTERVAL. SGPP1 was named alongside LPL, MBOAT7, LIPC, APOE-C1-C2-C4, and SPTLC3 as providing new biological insights at loci linked to cardiometabolic disease.

Reported associations

• Blood lipid metabolites: rs113338490 at the SGPP1 locus was associated with novel individual lipid species measured by mass spectrometry in both the South Asian PROMIS cohort (n=5,662) and the British INTERVAL cohort (n=13,814); the specific lipid species and per-variant effect sizes are not described in the available study text.
• Cardiometabolic disease loci: The locus was highlighted as one of several providing new biological insights in a study designed to investigate how individual lipid species contribute to cardiovascular and metabolic risk in an underrepresented South Asian population.

Evidence quality The single published lipidomics study enrolled 5,662 South Asian participants from PROMIS and 13,814 British participants from INTERVAL, for a combined sample of approximately 19,476 individuals analyzed using the same DIHRMS platform. SGPP1 was identified among 24 independent loci in PROMIS and 38 in INTERVAL. No p-values, odds ratios, or effect sizes specific to rs113338490 are provided in the available study text. Parallel analysis in two independent cohorts of distinct ancestry using the same analytical platform is a methodological strength. However, the absence of per-variant statistics and the lack of external replication outside these two cohorts limits interpretation. The study also explicitly notes the historical underrepresentation of South Asian populations in cardiovascular genetic studies, which gives the PROMIS arm particular context but also means findings require further validation. No conflicting studies were identified in the provided materials.

Tissue-specific expression effects

• WDR89: The alternate allele is associated with reduced expression in EBV-transformed lymphocytes (lab-grown immune cells), esophageal mucosa (the tissue lining the esophagus), subcutaneous adipose tissue (fat stored just under the skin), and sun-exposed lower leg skin GTEx Portal.
• ENSG00000274015 (uncharacterized gene): The alternate allele is associated with increased expression in tibial nerve, transverse colon, and cultured fibroblasts (connective tissue cells grown in a laboratory setting) GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.