Expressive

rs117542855 (FAM99A / KRTAP5-5): NAFLD Variant

Key takeaways

  • A related gene, FAM99B, shows reduced expression specifically in liver tissue for carriers of the alternate allele, according to GTEx functional data
  • This variant in the KRTAP5-5 / FAM99A region has been studied in connection with non-alcoholic fatty liver disease (NAFLD) using electronic health records from multiple US medical centers
  • The supporting GWAS enrolled both adults and children and included histological confirmation from liver biopsies in a subset of participants
  • Evidence linking this specific variant to NAFLD comes from a single study; independent replication has not been reported in the provided literature

Key takeaways

  • A related gene in the same family, FAM99B, shows reduced expression specifically in liver tissue for carriers of the alternate allele, according to GTEx functional data
  • This variant in the KRTAP5-5 / FAM99A region has been studied in connection with non-alcoholic fatty liver disease (NAFLD), a chronic liver condition estimated to affect 17-30% of adults in Western countries
  • The supporting GWAS enrolled both adults and children across multiple US medical centers and included histological confirmation from liver biopsies in a subset of participants
  • Evidence linking this specific variant to NAFLD derives from a single study; independent replication has not been reported in the provided literature

What the research says A genome-wide association study (GWAS) of NAFLD conducted across the Electronic Medical Records and Genomics (eMERGE) Network examined 1,106 adult cases and 8,571 controls, plus a pediatric sub-cohort of 396 cases and 846 controls, using natural language processing of clinical records alongside histological data from 235 liver biopsy samples to identify genetic contributors to this condition PMID 31159836. The study confirmed the established PNPLA3 cluster association, identified additional novel loci for NAFLD Activity Score (NAS) and liver fibrosis, and noted that NAFLD heritability estimates range from 20-70% depending on study design and ancestry PMID 31159836. GTEx v11 data from 953 donors show that the rs117542855 alternate allele is associated with reduced FAM99B expression in liver tissue (p = 6.9 × 10^-6), providing functional context at this locus GTEx Portal.

Reported associations

  • Non-alcoholic fatty liver disease (NAFLD): Locus examined in a multi-site GWAS of 1,106 cases and 8,571 controls (plus 1,242 pediatric participants) drawn from the eMERGE Network using NLP-derived case definitions from electronic medical records PMID 31159836
  • NAFLD Activity Score (NAS) and liver fibrosis: The same study performed case-only analyses using histological severity scores in 235 participants with liver biopsy data, examining associations with disease progression PMID 31159836

Evidence quality The sole association evidence comes from Namjou et al. 2019, an eMERGE GWAS of approximately 9,677 total participants across adult and pediatric sites PMID 31159836. No p-value or effect size specific to rs117542855 is reported in the available study excerpt; the paper's primary named hits are the PNPLA3 cluster (best p = 1.70 × 10^-²^0), a locus near IL17RA (p = 3.80 × 10^-8 for NAS score), and a locus near ZFP90-CDH1 (p = 2.74 × 10^-¹¹ for fibrosis) PMID 31159836. Whether the current locus reached genome-wide significance (conventionally p < 5 × 10^-8) cannot be determined from the provided text. No independent replication study is included. The GTEx eQTL signal for FAM99B in liver tissue (p = 6.9 × 10^-6, FDR < 0.05) provides suggestive functional context but is not itself a clinical association GTEx Portal. Overall, evidence for this locus should be considered preliminary.

Tissue-specific expression effects

  • FAM99B: Carriers of the rs117542855 alternate allele show reduced FAM99B expression specifically in liver tissue, based on GTEx v11 data from 953 donors (FDR < 0.05). Note: FAM99B is a distinct but closely related gene to the annotated FAM99A at this locus; the eQTL signal documented here is specific to FAM99B GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Lifestyle context

Concrete actions anchored to the cited research. We do not prescribe, we describe.

Diet

  • High-fructose corn syrup and refined carbohydrates Moderate

    High fructose intake drives hepatic lipid accumulation in NAFLD; particularly important for genetically predisposed individuals

    Minimize processed foods and sugary beverages; prioritize whole grains and complex carbohydrates

Discuss with your doctor

  • Genetic risk for nonalcoholic fatty liver disease Moderate

    T-allele carriers have 1.94-fold increased NAFLD odds per large GWAS; personalized management strategy needed

    Share rs117542855 T-allele status with physician for individualized NAFLD prevention strategy

Exercise

  • Regular aerobic exercise Moderate

    Physical activity improves insulin sensitivity and reduces hepatic fat content; key for NAFLD prevention

    Aim for at least 150 minutes of moderate-intensity aerobic activity per week

Lifestyle

  • Excessive alcohol consumption Moderate

    Alcohol exacerbates NAFLD risk; T-allele carriers have elevated baseline susceptibility

    Limit to no more than 1 drink per day for women or 2 per day for men

Screening

  • Nonalcoholic fatty liver disease assessment Moderate

    T risk allele associated with 1.94-fold increased odds of NAFLD in large GWAS study

    Discuss with physician about baseline liver imaging; consider ultrasound or transient elastography

Frequently asked questions

What is rs117542855?

rs117542855 is a genetic variant (a single nucleotide polymorphism, or SNP) located near the KRTAP5-5 and FAM99A genes. It has been studied in the context of non-alcoholic fatty liver disease (NAFLD), a condition in which excess fat builds up in the liver.

What does the FAM99A gene do?

FAM99A (Family with Sequence Similarity 99, Member A) is a gene whose precise biological function is not yet fully characterized. A closely related gene in the same family, FAM99B, shows reduced expression in liver tissue in carriers of the rs117542855 alternate allele according to GTEx data.

Is rs117542855 linked to fatty liver disease?

This variant has been examined in a genome-wide association study of NAFLD using data from the multi-site eMERGE Network. No specific p-value or effect size for this variant alone is available from the provided study summary, and independent replication has not been reported.

What is NAFLD?

Non-alcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver in people who drink little or no alcohol. It affects an estimated 17-30% of adults in Western countries and can progress to a more serious form involving liver inflammation and scarring.

What does the GTEx data show for this variant?

GTEx v11 data from 953 donors shows that the rs117542855 alternate allele is associated with reduced expression of FAM99B in liver tissue, meeting a false-discovery-rate threshold of under 5%. This is an eQTL (expression quantitative trait locus) - a statistical link between the variant and gene activity - not a direct measure of disease risk.