rs113300196 (TMEM167A): Cortical Folding Variant
Key takeaways
- rs113300196 is one of 856 loci significantly linked to sulcal depth - a measure of brain cortical folding - in a study of 33,748 people
- Sulcal depth is more genetically discoverable than cortical thickness or surface area, with an estimated 56% of variance under genetic control
- Gene-based analyses at this locus implicate neurodevelopmental pathways including neuronal proliferation, migration, and differentiation
- GTEx data links the variant's alternate allele to reduced expression of the nearby gene ENSG00000249664 in lung tissue
- Evidence comes from a single large study with partial cross-ancestry and cross-age generalization; independent replication for this locus has not yet been reported
Key takeaways
- rs113300196 is one of 856 loci reaching genome-wide significance for sulcal depth in a study of 33,748 UK Biobank participants
- Sulcal depth - a measure of how deeply the cerebral cortex folds - is more genetically discoverable than cortical thickness or surface area
- An estimated 56% of between-subject variance in sulcal depth is under genetic control, based on twin research cited in the source study
- Gene-based analyses across significant loci point to neurodevelopmental pathways including neuronal proliferation, migration, and differentiation
- GTEx data shows the variant's alternate allele is associated with reduced expression of the gene ENSG00000249664 in lung tissue
What the research says The first genome-wide association study (GWAS) of sulcal depth - a measure of cortical folding quantifying the convexity or concavity of any given point on the brain's surface - applied the multivariate omnibus statistical test (MOSTest) to vertex-wise brain imaging from 33,748 UK Biobank participants (mean age 64.3 years; 52% female) and identified 856 genome-wide significant loci (p < 5×10^-8), including rs113300196 at the ST13P12-TMEM167A locus. This locus exceeded the locus yield seen for cortical thickness (661 significant loci) and surface area (591 significant loci), with sulcal depth also showing higher heritability and effective sample size than either of those measures. Gene-based analyses indicated strong associations with neurodevelopmental processes, consistent with prior evidence that sulcal morphology is linked to neuronal proliferation, migration, and differentiation during brain development.
Reported associations
- Sulcal depth (cortical folding): rs113300196 is among 856 genome-wide significant loci (p < 5×10^-8) for sulcal depth, identified via MOSTest analysis of 1,153 vertex-wise cortical measurements in 33,748 UK Biobank participants; the study reports higher locus yield for sulcal depth than for either cortical thickness or surface area
Evidence quality The association derives from a single large discovery GWAS (n = 33,748 unrelated White British UK Biobank participants, mean age 64.3 years) using a multivariate vertex-wise approach. The study reports "acceptable rates of generalization" across two additional samples - 5,199 non-White-British UK Biobank participants and 8,072 younger adolescents (mean age 9.9 years) from the Adolescent Brain Cognitive Development (ABCD) study - which differ substantially from the discovery sample in ancestry and age, providing a partial cross-group robustness check. No dedicated independent large-scale replication for this specific locus is described in the provided text, and no PMID was assigned to the source study in the provided metadata. Evidence for rs113300196 should therefore be considered preliminary until confirmed in separate replication analyses.
Tissue-specific expression effects
- ENSG00000249664: The alternate allele is associated with reduced expression of this gene in lung tissue GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs113300196?
rs113300196 is a genetic variant located near the ST13P12 and TMEM167A genes. It was identified as statistically significant for sulcal depth - a measure of brain cortical folding - in a large genome-wide study of UK Biobank participants.
What is sulcal depth and why does it matter genetically?
Sulcal depth measures how deeply the brain's cortex folds into grooves called sulci. It reflects the primary folding pattern of the brain, is strongly heritable (estimated at ~56% from twin studies), and has been linked to neurodevelopmental processes as well as neurodevelopmental and neurodegenerative disorders.
What genes are near rs113300196?
The variant sits at the ST13P12 and TMEM167A locus. GTEx data additionally shows the variant's alternate allele is associated with reduced expression of a nearby gene (ENSG00000249664) in lung tissue.
Is rs113300196 linked to any brain conditions?
The available study links it to sulcal depth, a brain morphology measure associated with neurodevelopmental processes. No direct link to specific brain conditions is reported for this variant in the provided research.
How strong is the evidence for rs113300196 and brain folding?
It reached genome-wide significance (p < 5×10^-8) in a study of 33,748 UK Biobank participants, with some generalization shown in a non-White-British subsample and a younger adolescent cohort. Only a single discovery study is available, and independent large-scale replication for this specific locus has not yet been reported.