rs11068917 (TAOK3): Depression and Anxiety Variant

Key takeaways

• rs11068917, near the TAOK3 (Thousand and One Amino Acid Kinase 3) gene, has been identified in genome-wide studies of depressive symptoms, with roughly 72% of the identified variant set replicating in a cohort of approximately 1.9 million individuals.
• The locus has also been implicated in anxiety symptoms and in a composite well-being spectrum analysis spanning over 2.37 million participants.
• A loneliness GWAS meta-analysis of 511,280 individuals listed this locus among 19 genome-wide significant variants, with polygenic scores for loneliness associating with psychiatric and cardiovascular conditions.
• GTEx data shows the alternate allele is associated with reduced expression of nearby genes across at least seven tissue types, including heart, skeletal muscle, and thyroid.

What the research says A factor-analysis framework applied to 28 depression, anxiety, and neuroticism survey items in UK Biobank identified 89 independent variants for a latent depressive-symptom factor and 102 variants for an anxiety-symptom factor, with 72% and 78% respectively replicating in a separate cohort of approximately 1.9 million individuals with self-reported diagnoses PMID 34385698. A meta-analysis extending a loneliness GWAS to 511,280 subjects detected 19 significant variants from 16 loci, and polygenic scores derived from those results associated with cardiovascular, psychiatric, and metabolic conditions in electronic health record data PMID 32449928. Multivariate GWAS of the well-being spectrum (life satisfaction, positive affect, neuroticism, and depressive symptoms; N=2,370,390) identified 304 independent genome-wide significant signals, a 26% gain over four univariate analyses, with polygenic scores showing approximately 57% improved predictive power PMID 30858613.

Reported associations

• Depressive symptoms: Identified among 89 independent variants for a latent depressive-symptom genomic factor in UK Biobank; 72% of the full identified set replicated in an independent cohort of approximately 1.9 million individuals with self-reported depression PMID 34385698.
• Anxiety symptoms: Implicated in the anxiety-symptom factor (102 independent variants, 73 loci); 78% of that variant set replicated in the same large independent cohort PMID 34385698.
• Loneliness: Listed among 19 significant variants from 16 loci in a meta-analysis of 511,280 individuals; polygenic scores derived from this GWAS were associated with psychiatric, cardiovascular, and metabolic disorders in electronic health record data, and Mendelian randomization in the same study found evidence of a causal increasing effect of BMI and body fat on loneliness PMID 32449928.
• Well-being spectrum (life satisfaction, positive affect, neuroticism, and depressive symptoms combined): Included among 304 genome-wide significant signals from a multivariate GWAS in 2,370,390 individuals; enriched gene expression in brain subiculum and GABAergic interneurons was noted across the full signal set PMID 30858613.

Evidence quality Discovery sample sizes across the three source studies range from 511,280 to approximately 2.37 million participants, providing large statistical power PMID 32449928 PMID 30858613. The depression and anxiety study achieved 72% and 78% group-level replication in an independent cohort of approximately 1.9 million PMID 34385698. The well-being study reported a 26% increase in independent signals and approximately 57% improved polygenic score predictive power over univariate approaches PMID 30858613. No individual p-values or effect size estimates specific to rs11068917 are reported in the source study texts; all statistics describe the full genome-wide significant variant sets. No direct conflicts between studies were identified; the three papers address overlapping but phenotypically distinct constructs, and the high genetic correlations among depression, anxiety, neuroticism, and loneliness noted across them are mutually consistent.

Tissue-specific expression effects

• ENSG00000275759: The alternate allele of rs11068917 is associated with reduced expression of this gene across seven tissues: heart atrial appendage, sigmoid colon, thyroid, esophageal gastroesophageal junction, esophageal muscularis, tibial nerve, and skeletal muscle; the strongest single-tissue signal is in skeletal muscle (p=3.6e-58) GTEx Portal.
• ENSG00000275409: The alternate allele is associated with reduced expression of this gene in thyroid specifically (p=4.5e-40) GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.