rs10197940 (RIF1/TNFAIP6): Multi-tissue Expression Variant

Key takeaways

• rs10197940 reduces RIF1 gene expression across 8 tissues, including brain regions, arteries, nerves, skin, and fat, based on GTEx data from 953 donors.
• The strongest expression-reducing signal is in tibial nerve tissue (p=1.9x10^-50), and all 8 tissues show the same directional effect.
• The variant sits in the TNFAIP6 - RIF1 gene region; the available GTEx data reports eQTL effects specifically for RIF1.
• A large genome-wide association study of lung cancer in never-smoking Asian women provides research context for this gene region, though rs10197940 is not specifically named in that study's primary findings.
• No clinical disease associations or lifestyle factors have been linked to rs10197940 in the available study evidence.

What the research says The FLCCA (Female Lung Cancer Consortium in Asia) conducted a multistage GWAS (genome-wide association study, a scan of hundreds of thousands of genetic variants to identify those statistically associated with a disease) among never-smoking women in Asia, combining 5,510 lung cancer cases and 4,544 controls from 14 studies across mainland China, South Korea, Japan, Singapore, Taiwan, and Hong Kong, later expanded to 6,609 cases and 7,457 controls; the study identified three new lung cancer susceptibility loci, and rs10197940 was not specifically named among its primary findings in the provided text. GTEx v11 (Genotype-Tissue Expression) data from 953 donors identifies rs10197940 as a cis-eQTL for RIF1, meaning the variant is statistically associated with differences in RIF1 messenger RNA levels in tissue samples collected near the gene GTEx Portal. The alternate allele consistently reduces RIF1 expression across all 8 tested tissues, with p-values reaching as low as 1.9x10^-50 in tibial nerve GTEx Portal.

Reported associations

• RIF1 expression (multi-tissue eQTL): The alternate allele of rs10197940 is associated with reduced RIF1 gene expression across 8 tissues in GTEx v11 data from 953 donors, with effect sizes (on a log2-normalized scale) ranging from -0.21 to -0.34 and p-values as low as 1.9x10^-50 in tibial nerve tissue GTEx Portal.

Evidence quality The GTEx eQTL evidence is based on 953 donors across multiple tissues and shows highly consistent effects, with all 8 tested tissues showing reduced RIF1 expression and p-values spanning 1.5x10^-19 to 1.9x10^-50 GTEx Portal. The FLCCA lung cancer GWAS applied rigorous quality control with minimal genomic inflation (lambda = 1.014), identifying genome-wide significant associations at 10q25.2 (rs7086803, odds ratio 1.28, 95% CI 1.21-1.35, p=3.54x10^-18), 6q22.2 (rs9387478, odds ratio 0.85, 95% CI 0.81-0.90, p=4.14x10^-10), and 6p21.32 (rs2395185, odds ratio 1.17, 95% CI 1.11-1.23, p=9.51x10^-9) in a combined sample of 6,609 cases and 7,457 controls; rs10197940 was not named among the primary findings in the provided text. No replication studies, clinical outcome data, or functional validation experiments specific to rs10197940 are available in the provided materials, and the eQTL associations represent potential molecular mechanism rather than established clinical outcomes.

Tissue-specific expression effects

• RIF1: The alternate allele is associated with reduced expression in brain cortex (effect -0.34, p=3.9x10^-21), brain nucleus accumbens basal ganglia (effect -0.33, p=1.1x10^-19), aortic artery (effect -0.29, p=2.1x10^-26), tibial nerve (effect -0.29, p=1.9x10^-50), sun-exposed lower-leg skin (effect -0.26, p=3.6x10^-31), subcutaneous fat (effect -0.23, p=1.3x10^-25), non-sun-exposed suprapubic skin (effect -0.22, p=1.5x10^-19), and tibial artery (effect -0.21, p=1.3x10^-31), with the strongest statistical signal in tibial nerve GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.