280: SCD, FADS and a 3p25.2 (PPARG) locus shape fatty acid composition in human subcutaneous adipose tissue

Yan X et al., The American Journal of Human Genetics, Corrected proof. doi:10.1016/j.ajhg.2025.12.008 - In 569 TwinsUK subcutaneous adipose biopsies, twin models and GWAS identify SCD, FADS and 3p25.2 (PPARG) loci regulating fatty acid levels and conversions. Key terms: SCD, FADS1, PPARG, adipose-tissue, fatty-acids.

Study Highlights:
System and sample: 569 female TwinsUK subcutaneous adipose biopsies with matched serum, RNA-seq and 450K methylation data were analyzed. Key methods: gas chromatography fatty acid profiling, ACE twin heritability models, GWAS of 18 fatty acids and 15 product-to-precursor ratios, colocalization with adipose eQTLs and meQTLs, and polygenic score analysis. Main quantitative results: heritability of individual fatty acids ranged from 5%–59% while 15 fatty acid ratios were heritable and GWAS identified 10 genome-wide significant loci including SCD and FADS with the SCD lead variant explaining ~7–11% of variance and ratios showing heritability up to ~54%. Functional implication: colocalizations with adipose-specific eQTLs and meQTLs and associations between metabolic polygenic scores and fatty acid levels link local genetic regulation in adipose tissue to renal and cardio-metabolic phenotypes.

Conclusion:
Local genetic variation in adipose tissue, including SCD, FADS and a 3p25.2 locus near PPARG, regulates fatty acid composition and conversion and is connected to renal and cardio-metabolic traits.

Music:
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Article title:
Genetic regulation of fatty acid content in adipose tissue

First author:
Yan X

Journal:
The American Journal of Human Genetics, Corrected proof. doi:10.1016/j.ajhg.2025.12.008

DOI:
10.1016/j.ajhg.2025.12.008

Reference:
Yan X., Roberts A.L., El-Sayed Moustafa J.S., Villicaña S., Al-Hilal M., Tomlinson M., Menni C., Sanders T.A.B., Freidin M.B., Bell J.T., Small K.S., Genetic regulation of fatty acid content in adipose tissue. The American Journal of Human Genetics 113, 1–18, February 5, 2026. https://doi.org/10.1016/j.ajhg.2025.12.008

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/

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QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-02-04.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited substantive scientific claims regarding adipose fatty acid heritability and tissue specificity, GWAS loci (SCD, FADS, 3p25.2/PPARG), adipose molecular mechanisms (eQTL/meQTL colocalization), the fat–kidney link via pleiotropy, and polygenic-score associations with adipose fatty acids; also covered study limitat
- transcript topics: Adipose fatty acid heritability and tissue specificity; Genome-wide association signals for adipose fatty acids (SCD, FADS, 3p25.2/PPARG); Adipose-specific regulation and colocalization with eQTL/meQTL; Arachidonic acid and kidney trait pleiotropy; Polygenic scores and adipose fatty acids; Limitations and demographic scope

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 8
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article...