rs10198175 (APOB): Bipolar Disorder and Binge Eating
Key takeaways
- rs10198175 sits downstream of APOB (apolipoprotein B) and near LINC02850, a long non-coding RNA.
- A genome-wide study found this variant among top signals for bipolar disorder in people with a lifetime history of binge eating.
- Of two nearby APOB-region variants tested, rs10198175 specifically replicated in an independent cohort and in a combined meta-analysis.
- GTEx data link this variant to reduced GDF7 expression in the adrenal gland.
- Evidence is preliminary; cohorts are modest in size and no causal pathway has been established.
Key takeaways
- rs10198175 sits downstream of APOB (apolipoprotein B) and near LINC02850 (long intergenic non-coding RNA 2850).
- A genome-wide association study found this variant among the top-ranked signals for bipolar disorder (BD) specifically in participants with a lifetime history of binge eating (BE).
- Of two nearby APOB-region variants identified in that study, rs10198175 was the one that showed replication support in a second independent cohort and in a combined meta-analysis.
- GTEx data link the variant to reduced GDF7 expression in the adrenal gland.
- Evidence is preliminary; both cohorts are modest in size by current GWAS standards and no causal mechanism has been established.
What the research says rs10198175, located downstream of APOB (apolipoprotein B) and near LINC02850, was identified as a top-ranked signal in a GWAS of BD subtypes stratified by lifetime binge eating history, using a European American discovery cohort of 1,001 BD cases and 1,034 controls genotyped at 729,454 SNPs PMID 25193798. This locus specifically showed replication support in an independent cohort of 855 cases and 857 controls, and in a meta-analysis combining both samples PMID 25193798.
Reported associations
- Bipolar disorder with comorbid binge eating history: rs10198175 was a top-ranked discovery signal (1,001 BD cases, 1,034 controls) comparing BD cases with versus without lifetime binge eating comorbidity, with replication support in a second cohort (855 cases, 857 controls) and in a meta-analysis of both samples PMID 25193798.
Evidence quality The primary evidence for this locus comes from a single GWAS with a discovery cohort of 1,001 European American BD cases and 1,034 controls, replicated in an independent sample of 855 cases and 857 controls PMID 25193798. Both cohorts were limited to European Americans, constraining generalizability. The variant was described as top-ranking; exact genome-wide significance thresholds for this specific SNP are not reported in the available study text. A key limitation acknowledged by the authors is that binge eating history was not collected from controls, making it unclear whether the association reflects a general binge eating risk factor or a subtype of BD defined by this comorbidity. By contemporary GWAS standards, these sample sizes are modest, and replication in large, diverse populations has not been reported in the provided sources. This evidence should be considered preliminary.
Tissue-specific expression effects
- GDF7: The alternative allele is associated with reduced GDF7 expression in the adrenal gland (p = 1.6e-5) GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs10198175?
rs10198175 is a single nucleotide polymorphism (a location in the genome where one DNA letter varies between people) found downstream of the APOB gene and near LINC02850. It has been studied as a candidate risk signal for bipolar disorder in people with a lifetime history of binge eating.
What is APOB and why is it relevant here?
APOB (apolipoprotein B) is a gene involved in lipoprotein metabolism that has been studied in genome-wide analyses of circulating fatty acid levels and lipid traits. In the context of this variant, it was identified as the nearest protein-coding gene to rs10198175 in a genetic study of bipolar disorder subtypes.
Is rs10198175 associated with bipolar disorder?
A genome-wide study found rs10198175 among the top signals for bipolar disorder specifically in participants with a lifetime history of binge eating, with the finding replicated in an independent cohort and in a meta-analysis. Evidence is preliminary and both cohorts were limited to European Americans.
Why does binge eating history change the association?
The study stratified bipolar disorder cases by whether they had a lifetime history of binge eating, rather than analyzing all bipolar cases together. The authors noted that this subgroup approach can improve statistical power by reducing heterogeneity among cases.
What does GTEx data show for this variant?
GTEx data indicate that the alternative allele of rs10198175 is associated with reduced GDF7 expression in the adrenal gland. The clinical significance of this expression change is not yet established.