rs10013352 (LRBA): Brain and Nerve Gene Expression
Key takeaways
- The ALT allele of rs10013352 increases LRBA expression in brain cerebellum, brain hypothalamus, and tibial nerve based on GTEx data from 953 donors
- Four other nearby genes show expression changes in spleen, nerve, heart, and lymphocyte tissues driven by the same allele
- This locus appears in a multi-ancestry GWAS on tobacco and alcohol use behaviors covering 3.4 million people
- These are gene expression associations, not direct measures of disease risk or trait outcomes
Key takeaways
- The ALT allele of rs10013352 is associated with increased LRBA expression in brain regions and tibial nerve based on GTEx v11 data from 953 donors
- Expression changes were also detected in four nearby genes (FHIP1A, MAB21L2, DCLK2, and RPS3A) across spleen, tibial nerve, heart, and lymphocyte tissues
- This locus appears in a large multi-ancestry genome-wide association study on tobacco and alcohol use behaviors covering approximately 3.4 million individuals
- These are gene expression associations, not direct measures of disease risk or trait outcomes
What the research says GTEx v11 eQTL (expression quantitative trait locus) data from 953 donors show that the ALT allele (the alternative form of the variant) of rs10013352 increases LRBA expression in brain cerebellum (slope +0.26), brain hypothalamus (slope +0.20), tibial nerve (slope +0.17), and cultured fibroblasts (slope +0.13) GTEx Portal. The same allele is associated with reduced FHIP1A expression in spleen (slope -0.38), increased MAB21L2 expression in tibial nerve (slope +0.24), reduced DCLK2 expression in heart atrial appendage (slope -0.17), and reduced RPS3A expression in EBV-transformed lymphocytes (slope -0.15) GTEx Portal. This locus is included among 2,143 associated loci and 3,823 independently associated variants from a multi-ancestry GWAS (genome-wide association study) on tobacco and alcohol use behaviors in approximately 3.4 million individuals (Saunders et al., Nature 2023).
Reported associations
- LRBA expression - Brain Cerebellum: ALT allele linked to increased expression (slope +0.26, p=1.6e-6) GTEx Portal
- LRBA expression - Brain Hypothalamus: ALT allele linked to increased expression (slope +0.20, p=1.2e-4) GTEx Portal
- LRBA expression - Tibial Nerve: ALT allele linked to increased expression (slope +0.17, p=1.2e-10) GTEx Portal
- LRBA expression - Cultured Fibroblasts: ALT allele linked to increased expression (slope +0.13, p=2.9e-6) GTEx Portal
- FHIP1A expression - Spleen: ALT allele linked to reduced expression (slope -0.38, p=3.3e-5) GTEx Portal
- MAB21L2 expression - Tibial Nerve: ALT allele linked to increased expression (slope +0.24, p=7.5e-5) GTEx Portal
- DCLK2 expression - Heart Atrial Appendage: ALT allele linked to reduced expression (slope -0.17, p=5.5e-5) GTEx Portal
- RPS3A expression - EBV-transformed Lymphocytes: ALT allele linked to reduced expression (slope -0.15, p=4.6e-5) GTEx Portal
Evidence quality All eQTL associations are drawn from GTEx v11 (953 donors), with all listed effects passing a false discovery rate threshold below 0.05; slope values are log2-normalized effect sizes representing the estimated change in gene expression per copy of the ALT allele GTEx Portal. The most statistically robust association for this gene in these eQTL data is in tibial nerve (p=1.2e-10), followed by brain cerebellum (p=1.6e-6) and cultured fibroblasts (p=2.9e-6). No conflicting eQTL findings are reported in the provided data. The multi-ancestry GWAS (Saunders et al., Nature 2023; approximately 3.4 million individuals, 2,143 loci identified) situates this locus in research on tobacco and alcohol use, but the specific phenotype association for rs10013352 is not named in the study text provided, so trait-level evidence for this variant is incomplete from available sources.
Tissue-specific expression effects
- LRBA: increased expression in brain cerebellum, brain hypothalamus, tibial nerve (strongest association among listed tissues), and cultured fibroblasts GTEx Portal
- FHIP1A: reduced expression in spleen GTEx Portal
- MAB21L2: increased expression in tibial nerve GTEx Portal
- DCLK2: reduced expression in heart atrial appendage GTEx Portal
- RPS3A: reduced expression in EBV-transformed lymphocytes GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is LRBA and what does rs10013352 do to it?
LRBA is the primary gene at the rs10013352 locus. GTEx data show that the ALT allele of this variant is associated with higher LRBA gene activity in brain regions and peripheral nerve tissue, suggesting the variant influences how much LRBA is expressed in those locations.
What does rs10013352 do?
Based on GTEx v11 data from 953 donors, the ALT allele of rs10013352 is linked to increased LRBA expression in brain and nerve tissue, and to expression changes in four other nearby genes across spleen, heart atrial appendage, tibial nerve, and lymphocyte tissues.
Is rs10013352 linked to smoking or alcohol use?
This locus appears among variants studied in a large multi-ancestry GWAS on tobacco and alcohol use behaviors covering 3.4 million individuals (Saunders et al., Nature 2023). The specific trait association for rs10013352 is not detailed in the available study text, so the connection is preliminary based on available materials.
What is an eQTL and why does it matter for this variant?
An eQTL (expression quantitative trait locus) is a genetic variant associated with differences in how much a gene is expressed in a particular tissue. For rs10013352, eQTL data show it is linked to gene expression changes in at least five genes across seven tissue and cell types, describing biological mechanism rather than predicting health outcomes directly.
Which tissues are affected by rs10013352?
GTEx data show expression effects in multiple tissue and cell types, including brain cerebellum, brain hypothalamus, tibial nerve, cultured fibroblasts, spleen, heart atrial appendage, and EBV-transformed lymphocytes.