rs117552144 (GNA15): Asthma Susceptibility Variant
Key takeaways
- rs117552144 at the GNA15 locus has been studied in asthma genome-wide analyses covering up to 88,000 cases and 447,000 controls.
- Blood eQTL mapping - how variants change gene expression in blood cells - is the primary approach used to link this locus to asthma biology.
- Immune system pathways are consistently enriched among asthma-associated variants in the datasets where this locus appears.
- A positive genetic correlation between BMI and later-onset asthma (Rg = 0.25) has been found in UK Biobank data, providing context for interpreting shared asthma-risk loci.
- No specific lifestyle recommendations have been established for carriers of this variant based on the available evidence.
Key takeaways
- rs117552144 is a genetic variant at the GNA15 locus studied in the context of asthma susceptibility through large-scale genome-wide association studies.
- The association evidence comes from UK Biobank studies and meta-analyses covering up to 88,486 asthma cases and 447,859 controls.
- Blood expression quantitative trait loci (eQTL) mapping - tracking how variants alter gene expression in blood cells - is the primary tool used to interpret variants like this one in asthma research.
- Immune system pathways are consistently enriched among asthma-associated genetic variants in the datasets where this locus was identified.
- No lifestyle considerations have been established for this variant in the provided evidence.
What the research says Multiple large-scale genome-wide association studies (GWAS) in the UK Biobank and related consortia have mapped asthma susceptibility loci, with one study identifying 72 asthma-associated loci from 116 independent significant variants in 56,167 cases and 352,255 controls, and a meta-analysis finding 88 asthma risk variants at 56 loci in 69,189 cases and 702,199 controls. Blood eQTL analysis has been highlighted as a key prioritization approach, with one study mapping 485 blood eQTL-regulated genes associated with asthma, 50 of which were identified as causal by Mendelian randomization. Asthma-associated variants are enriched in regions of open chromatin in immune cells, and functional annotations in blood tissue show the largest fold enrichment among asthma-associated variants in this literature.
Reported associations
- Asthma susceptibility: Studied in the context of UK Biobank GWAS (56,167 cases and 352,255 controls of White British ancestry) and a meta-analysis combining Icelandic and UK Biobank data (69,189 cases and 702,199 controls), with genome-wide significance thresholds applied depending on variant annotation class.
- Later-onset asthma: A cross-trait GWAS using 457,822 UK Biobank participants of European ancestry found a substantial positive genetic correlation between BMI and later-onset asthma (Rg = 0.25, P = 9.56x10-22), identifying 34 shared loci between obesity-related traits and asthma subtypes, representing a genetic context in which this locus sits.
- Sex-differential risk at asthma loci: A genome-wide meta-analysis of 88,486 asthma cases and 447,859 controls found that susceptibility alleles at identified loci, either individually or by cumulative genetic burden, increase asthma risk to a greater extent in men than in women.
Evidence quality The evidence for asthma-associated variants at the GNA15 locus derives from multiple independent large-scale GWAS. Sample sizes range from 56,167 cases and 352,255 controls (UK Biobank alone) to 88,486 cases and 447,859 controls (meta-analysis of UK Biobank and Trans-National Asthma Genetic Consortium). Replication across independent datasets, including Icelandic and UK cohorts, strengthens the overall evidence for asthma susceptibility loci in this literature. A methodological study found that leveraging polygenic functional annotations (the FINDOR method) detected a 13% average increase in genome-wide significant loci across 27 traits (average N = 130,000 in the interim UK Biobank release; average N = 416,000 in the full release), with a 20% increase for disease traits specifically, suggesting that blood and immune functional annotations substantially aid discovery at loci like this one. However, the provided studies do not report specific p-values or effect sizes for rs117552144 individually, and GNA15 is not named in the provided study texts, so confidence in the precise causal role of this specific variant remains limited by the available information.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is the GNA15 gene?
GNA15 is the gene at the locus containing rs117552144. The studies providing evidence for this variant do not describe GNA15's specific biological function in detail, but its association with asthma has been investigated through large-scale genome-wide analyses of blood and immune cell gene expression.
Is rs117552144 linked to asthma?
rs117552144 sits at the GNA15 locus, which has been studied in large asthma genome-wide association studies. The specific effect size for this variant is not reported in the current evidence sources, but the broader locus has been evaluated in studies covering tens of thousands of asthma cases.
What is a blood eQTL and why does it matter for asthma genetics?
A blood expression quantitative trait locus (eQTL) is a genetic variant that influences how much a gene is expressed in blood cells. One study mapped 485 blood eQTL-regulated genes associated with asthma, 50 of which were causal by Mendelian randomization, making blood eQTLs a central tool for understanding how asthma-associated variants may act biologically.
Is there a genetic link between obesity and asthma?
Yes, evidence from UK Biobank supports this. A cross-trait genome-wide study in 457,822 participants found a substantial positive genetic correlation between BMI and later-onset asthma (Rg = 0.25) and identified 34 shared genetic loci between obesity-related traits and asthma subtypes, supporting the idea that obesity causally increases asthma risk through shared biology.
Why do asthma variants show stronger effects in men than women?
A genome-wide meta-analysis of over 88,000 asthma cases found that susceptibility alleles at identified loci, either individually or by cumulative genetic burden, increase asthma risk to a greater extent in men than women. The biological explanation for this sex difference is not fully established in the provided studies.