rs10750165 (NECTIN1-DT): ADHD Aggressiveness Variant
Key takeaways
- rs10750165 sits near NECTIN1-DT, a long noncoding RNA gene with expression detected across multiple brain regions.
- A GWAS of 1,060 adults with ADHD found suggestive signals at this locus, but none reached genome-wide significance.
- Suggestive GWAS signals showed significant enrichment in defiant/vindictive and irritable dimensions of oppositionality in childhood ADHD.
- GTEx v11 data link rs10750165 to increased NECTIN1-DT expression and reduced expression of two nearby genes in cortical brain tissue.
- All associations are preliminary and have not been independently replicated.
Key takeaways
- rs10750165 sits near NECTIN1-DT, a long noncoding RNA gene with expression detected across multiple brain regions including the cortex and frontal cortex.
- A genome-wide association study (GWAS) of 1,060 adults with ADHD found suggestive signals at this locus, but none reached the standard genome-wide significance threshold (P < 5×10^-8).
- Suggestive GWAS signals showed significant enrichment in defiant/vindictive and irritable dimensions of oppositionality in childhood ADHD.
- GTEx v11 data link rs10750165 to increased NECTIN1-DT expression in several brain regions and to reduced expression of two nearby genes in cortical tissue.
- All associations are preliminary and have not been independently replicated.
What the research says A genome-wide association study enrolled 1,060 adults with attention deficit hyperactivity disorder (ADHD) to examine genetic contributions to childhood aggressiveness; no single variant reached genome-wide significance (P < 5×10^-8), placing all findings in the suggestive category. Enrichment analyses further linked the sub-threshold signals to the defiant/vindictive dimension of oppositionality in childhood ADHD (Fisher's P = 2.28×10^-6) and the irritable dimension (Fisher's P = 0.0061), providing contextual support but not confirmation of any individual variant. GTEx v11 cis-eQTL analyses - which test whether a variant statistically correlates with nearby gene expression levels across tissues - identify rs10750165 as associated with increased NECTIN1-DT expression and reduced expression of two neighboring genes in cortical brain regions GTEx Portal.
Reported associations
- Childhood aggressiveness in ADHD (suggestive): A GWAS of 1,060 adult ADHD patients detected sub-threshold signals at this locus; the study-wide signals showed enrichment in defiant/vindictive oppositionality (Fisher's P = 2.28×10^-6) and irritable oppositionality (Fisher's P = 0.0061) in childhood ADHD, but no genome-wide significant result was reported.
- NECTIN1-DT expression in brain and heart: The ALT allele is associated with increased expression of this lncRNA in Brain Anterior Cingulate Cortex (Brodmann area 24), Brain Cortex, Brain Frontal Cortex (Brodmann area 9), Brain Spinal Cord (cervical c-1), and Heart Atrial Appendage GTEx Portal.
- ENSG00000287545 cortical expression: The ALT allele is associated with reduced expression of this neighboring gene in Brain Cortex GTEx Portal.
- ENSG00000288047 cortical expression: The ALT allele is associated with reduced expression of this neighboring gene in Brain Frontal Cortex (Brodmann area 9) and Brain Cortex GTEx Portal.
Evidence quality The only clinical genetic association evidence comes from a single GWAS of 1,060 adult ADHD patients - a modest sample by contemporary standards - and no variant reached genome-wide significance; all associations at this locus remain exploratory and have not been replicated in an independent cohort. Enrichment analyses provided contextual support by showing that sub-threshold signals from the adult ADHD study overlapped with dimensions of oppositionality in childhood ADHD, but enrichment tests characterize signal overlap across sets of variants, not individual-variant validity. The GTEx eQTL data are based on 953 donors across 54 tissues and meet FDR < 0.05, establishing statistically robust expression correlations GTEx Portal; however, eQTL associations reflect correlation with gene expression and do not demonstrate functional or clinical consequence.
Tissue-specific expression effects
- ENSG00000287545: Reduced expression in Brain Cortex with the ALT allele GTEx Portal.
- ENSG00000288047: Reduced expression in Brain Frontal Cortex (Brodmann area 9) and Brain Cortex with the ALT allele GTEx Portal.
- NECTIN1-DT: Increased expression in Brain Anterior Cingulate Cortex (Brodmann area 24), Brain Cortex, Brain Frontal Cortex (Brodmann area 9), Brain Spinal Cord (cervical c-1), and Heart Atrial Appendage with the ALT allele GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is NECTIN1-DT?
NECTIN1-DT is a long noncoding RNA gene - a region of DNA that produces RNA but no protein. GTEx data show it is expressed in several brain regions, including the cortex, frontal cortex, and anterior cingulate cortex, as well as in heart atrial tissue.
Is rs10750165 linked to ADHD or aggression?
A genome-wide association study found suggestive signals near this locus in 1,060 adults with ADHD, and those signals showed enrichment in defiant/vindictive and irritable dimensions of oppositionality. However, no result reached genome-wide significance and independent replication has not been reported.
What does rs10750165 do to gene expression in the brain?
GTEx v11 data show the ALT allele is associated with increased NECTIN1-DT expression and reduced expression of two nearby genes in brain cortical regions. These are expression correlations observed in post-mortem tissue samples, not direct measures of brain activity.
Has rs10750165 been confirmed by multiple studies?
No. Only one GWAS examining this locus in the context of ADHD aggressiveness is described in the available literature, and its findings are below genome-wide significance. The evidence is exploratory and requires replication.
Which brain regions are affected by rs10750165?
GTEx eQTL data link rs10750165 to expression changes in Brain Cortex, Brain Frontal Cortex (Brodmann area 9), Brain Anterior Cingulate Cortex (Brodmann area 24), and Brain Spinal Cord (cervical c-1). These associations are derived from post-mortem tissue samples across 953 donors.