rs10831415 (FAM76B): Substance Use Disorder Risk
Key takeaways
- rs10831415 sits in the LNCRNA-IUR/FAM76B region and was linked to shared risk across four substance use disorders in a large cross-ancestry genetic study.
- The variant shows the same risk direction for alcohol, cannabis, opioids, and tobacco, pointing to a common biological pathway rather than substance-specific effects.
- Genes at this locus are most active in addiction-linked brain regions including the amygdala, cortex, and hippocampus.
- Individuals in the top 10% of polygenic risk scores built from variants like this one had roughly 2 to 3 times the odds of developing a substance use disorder.
- The evidence comes from a single large meta-analysis and the finding for this specific variant should be considered preliminary until independently replicated.
Key takeaways
- rs10831415 maps to the LNCRNA-IUR / FAM76B region and was identified as a substance-use-disorder-associated locus in the largest cross-ancestry genetic meta-analysis of its kind to date.
- The variant shows a concordant (same-direction) effect across alcohol, cannabis, opioid, and tobacco use disorders, suggesting it tags a shared biological risk pathway rather than a single-substance mechanism.
- Genes identified alongside this locus are predominantly expressed in neuronal cells of addiction-relevant brain regions, including the amygdala, cortex, and hippocampus.
- Polygenic scores built from concordant variants like this one placed individuals in the top decile at roughly 2-3 times the odds of developing a substance use disorder.
What the research says rs10831415 - located in the LNCRNA-IUR / FAM76B region - was identified as one of 220 genomic loci (40 of them novel, meaning not previously reported in any genome-wide association study of substance use) with concordant associations across multiple substance use disorders (SUDs) in a genome-wide meta-analysis covering European-, African-, and American-mixed-ancestry populations. Concordant variants as a class collectively explained 56-96% of the SNP-heritability (the portion of trait variance attributable to common genetic variants) of each individual SUD in the European-ancestry-like sample, and individuals in the top 10% of polygenic scores derived from these variants had odds ratios of 1.95-2.87 for developing an SUD. Gene mapping and prioritization across this meta-analysis identified 785 SUD-shared genes, predominantly expressed in neuronal cells of the amygdala, cortex, hippocampus, hypothalamus, and thalamus.
Reported associations
- Cross-substance use disorder risk: rs10831415 shows a same-direction association across alcohol, cannabis, opioid, and tobacco use disorders in diverse ancestry populations. Concordant variants as a class explained 56-96% of the SNP-heritability of each SUD in the European-ancestry-like sample of the identifying meta-analysis. The individual effect size for this specific variant is not reported in the available study text.
Evidence quality The evidence for rs10831415 derives from a single large-scale cross-SUD genome-wide meta-analysis described as the largest of its kind, incorporating samples genetically similar to European, African, and American-mixed reference populations and identifying 220 loci and 785 SUD-shared genes in total. While the study scale is substantial, the individual p-value and effect size for rs10831415 specifically are not reported in the available study text - only class-level statistics (56-96% SNP-heritability explained; OR 1.95-2.87 in the top decile) are reported for concordant variants as a whole. No PMID was available for this publication in the provided source material, and no independent replication of this specific variant in a separate cohort is documented in the available studies. The finding should therefore be treated as preliminary until confirmed in independent datasets.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs10831415?
rs10831415 is a genetic variant located in the LNCRNA-IUR/FAM76B genomic region. It was identified in a large genome-wide meta-analysis as one of over 200 loci associated with shared risk across multiple substance use disorders.
What is the FAM76B gene?
FAM76B (Family with Sequence Similarity 76, Member B) is a gene located near a long non-coding RNA region called LNCRNA-IUR. Its precise biological role in substance use is not yet fully characterized, but it was flagged as a shared genetic signal across alcohol, cannabis, opioid, and tobacco use disorders in a large genetic meta-analysis.
Is rs10831415 linked to addiction?
A large genetic meta-analysis found this variant to be associated with substance use disorders spanning alcohol, cannabis, opioids, and tobacco. The variant showed the same risk direction for each condition, suggesting it may influence a shared biological pathway rather than being specific to one substance.
What does it mean that this variant is concordant across substances?
Concordant means the variant pushes risk in the same direction for every substance studied - if it increased risk for alcohol use disorder, it also increased risk for cannabis, opioid, and tobacco use disorders. This pattern suggests the variant influences a common biological mechanism underlying multiple forms of substance use disorder, rather than acting through substance-specific pathways.
How strong is the evidence for rs10831415?
The evidence comes from a single large cross-ancestry meta-analysis described as the largest cross-substance use disorder study of its kind. However, the individual effect size and statistical significance for rs10831415 specifically have not been published in available materials, and independent replication of this variant has not been reported. The finding should be treated as preliminary.