320: Sex-stratified cQTL mapping identifies TOX (IFN-γ) and EGFR (IL-10) regulators in Dutch and Tanzanian cohorts

Amour C et al., Human Genetics and Genomics Advances, Journal Pre-proof - Sex-stratified cQTL mapping in Tanzanian and Dutch adults identifies sex-specific regulators such as TOX-linked IFN-γ in males and EGFR-linked IL-10 in females, revealing multiple genome-wide cQTLs. Key terms: TOX, EGFR, cytokine QTL, sex-stratified GWAS, Tanzania-Netherlands.

Study Highlights:
The study analyzed cytokine production after ex vivo stimulation in two human cohorts (Tanzania 300TZFG and Dutch 500FG) using sex-stratified cytokine QTL mapping with linear models adjusted for cell counts and covariates. Genotyping, imputation, ELISA cytokine assays, colocalization (coloc) and SNP×sex interaction tests were applied to test sex-specific genetic effects. The authors report twelve genome-wide significant cQTLs in the Tanzanian cohort (seven male-specific, five female-specific) and twelve in the Dutch cohort with multiple sex-specific loci, highlighting TOX-associated IFN-γ regulation in males and EGFR-linked IL-10 regulation in females. These sex-specific autosomal effects altered which associations were detectable in pooled analyses, implying implications for sex-aware precision approaches to immune-related diseases.

Conclusion:
Sex-stratified autosomal analyses identify distinct genetic regulators of cytokine production, demonstrating that many cQTLs act in a sex-specific manner across Tanzanian and Dutch cohorts and can be missed by pooled analyses.

Music:
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Article title:
Sex-stratified genetic regulators of cytokine production in the Dutch and Tanzanian populations

First author:
Amour C

Journal:
Human Genetics and Genomics Advances, Journal Pre-proof

DOI:
10.1016/j.xhgg.2026.100593

Reference:
Amour C, Cetatean R, Ponce IR, Keur N, Temba GS, Kullaya VI, Mmbaga BT, Kavishe R, Joosten LAB, Netea MG, de Mast Q, Boahen CK, Kumar V, Sex-stratified genetic regulators of cytokine production in the Dutch and Tanzanian populations, Human Genetics and Genomics Advances (2026), doi: https://doi.org/10.1016/j.xhgg.2026.100593.

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QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-03-19.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the transcript sections describing (1) Tanzanian cohort results (12 cQTLs; 7 male-specific, 5 female-specific), (2) Dutch cohort results (12 cQTLs; 6 male-specific, 6 female-specific), (3) exemplar sex-specific loci TOX (male IFN-γ) and EGFR (female IL-10), (4) CNTNAP2 and ANXA8 findings, (5) colocalization ana
- transcript topics: Sex differences in immune regulation and cytokine signaling; Cohort design: Tanzanian (TZ) and Dutch (NL) sex-stratified cQTL mapping; TOX locus and IFN-γ response in males (S. pneumoniae); EGFR locus and IL-10 response in females (C. burnetii); CNTNAP2 locus and IFN-γ response in females (M. tuberculosis).; ANXA8 locus and TNF-α response in females (C. albicans)

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 6
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- Two cohorts: Tanzania TZFG and Netherlands 500FG (Dutch) with sex-stratified cQTL mapping
- Tanzanian cohort identified 12 genome-wide significant cQTLs (7 male-specific, 5 female-specific)
- Dutch cohort identified 12 genome-wide significant cQTLs (6 male-specific, 6 female-specific)
- TOX locus variant rs10092649 associated with IFN-γ production after S. pneumoniae stimulation in males
- EGFR-proximal locus rs79030770 associated with IL-10 production after C. burnetii stimulation in females
- CNTNAP2 locus variant rs17170577 associated with IFN-γ production after M. tuberculosis stimulation in females

QC result: Pass.