Neurology & Cognition

Key neurotrophin variant that controls activity-dependent BDNF release, affecting memory consolidation, neuroplasticity, and stress resilience

Influences episodic memory performance and hippocampal function through the KIBRA protein's role in synaptic plasticity

Intronic variant in the calsyntenin-2 gene associated with episodic memory performance and hippocampal inhibitory circuit function

Second strongest genetic risk factor for Alzheimer's disease after APOE, associated with increased tau pathology and accelerated cognitive decline

Intronic variant in clusterin gene affecting Alzheimer's disease risk through regulation of amyloid-beta clearance

Rare missense variant in microglial receptor TREM2 that significantly increases late-onset Alzheimer's disease risk through impaired microglial function and amyloid clearance

Variant in the PICALM gene affecting amyloid-beta clearance across the blood-brain barrier and Alzheimer's disease risk

Parkinson's disease GWAS risk variant affecting alpha-synuclein expression and neuronal differentiation

Intronic SNCA variant (intron 4) associated with Parkinson's disease risk and cognitive impairment; the G allele upregulates alpha-synuclein protein levels and is independent of rs356219

SNCA 3′-region variant in the extended 3′ UTR that affects alpha-synuclein mRNA stability and expression, consistently associated with Parkinson's disease risk across Asian and European populations

SNCA upstream regulatory variant (near gene-5) that is part of the 4-SNP SNCA risk haplotype (OR 2.51 for PD) and shows an independent TT homozygote association with Parkinson's disease risk and cognitive impairment

Haplotype-tagging variant distinguishing MAPT H1 and H2 clades, affecting risk for Parkinson disease, progressive supranuclear palsy, and other tauopathies

Intronic MAPT variant that regulates tau exon 3 splicing via hnRNP F/Q binding, distinguishing H1 (risk) from H2 (protective) haplotypes for Parkinson's disease, PSP, corticobasal degeneration, and Alzheimer's disease

Intronic MAPT variant tagging the H1c sub-haplotype within the H1 clade, independently elevating risk for progressive supranuclear palsy and corticobasal degeneration through increased 4-repeat tau expression

Intronic MAPT variant whose T allele co-defines the H1c sub-haplotype, independently conferring OR 1.85 for progressive supranuclear palsy and OR 2.07 for corticobasal degeneration in the same meta-analysis validating rs242557

Intronic MAPT variant that directly regulates tau exon 3 splicing via differential hnRNP F/Q binding; the G allele (H1 haplotype) reduces exon 3 inclusion, elevating 4-repeat tau isoforms and increasing risk for Parkinson's disease, PSP, and corticobasal degeneration

Intronic MAPT variant whose A allele defines the H1h sub-haplotype — a configuration distinct from H1c — independently associated with non-tremor dominant Parkinson's disease at OR 2.9 after Bonferroni correction, and sharing no meaningful linkage disequilibrium with the H1c-defining markers rs242557 or rs2471738 (r² ≈ 0.01)

SNCA 3′-region regulatory variant that upregulates alpha-synuclein expression and independently increases Parkinson's disease risk, earlier onset, and cognitive decline

Common noncoding variant upstream of LRRK2 that increases gene expression in microglia and Parkinson's disease risk

Common variant in the Nav1.7 sodium channel affecting pain sensitivity and pain threshold

Capsaicin receptor variant affecting heat and pain sensitivity

Promoter variant affecting GTP cyclohydrolase 1 expression and pain sensitivity, with opposite effects in European vs African populations

Intronic variant affecting thermal pain sensitivity and central pain signal transmission

Upstream regulatory variant of the cold-sensing TRPM8 channel that modulates migraine susceptibility, cold pain sensitivity, and brown adipose thermogenesis

Loss-of-function variant in the P2X7 receptor that reduces inflammatory response and may modulate pain sensitivity

Gain-of-function missense variant in the P2X7 ATP-gated receptor that increases receptor expression and ion channel activity, heightening neuroinflammation and linked to mood disorders, pain sensitization, and infection severity

Gain-of-function variant in the P2X7 receptor that increases ATP-gated pore formation, IL-1β release, and microglial neuroinflammation, associated with mood disorders and chronic pain severity

P2RX7 variant with a unique dual mechanism — gain-of-function in channel opening and loss-of-function in pore formation — associated with chronic pain susceptibility, neuroinflammation, and modulation of microglial signaling

Missense variant in the C-terminal domain of the P2X7 receptor that disrupts normal receptor dimerisation when coexpressed with the wild-type allele, with the G (Arg460) allele associated with major depressive disorder in a large meta-analysis and with higher multiple sclerosis severity scores; the A (Gln460, low-activity) allele is independently linked to rapid cycling in bipolar disorder

The most common cause of autosomal recessive nonsyndromic hearing loss in Europeans; homozygous deletion eliminates connexin 26 function and causes severe-to-profound congenital deafness

Connexin 26 missense variant causing partial loss of cochlear gap junction function; the leading cause of mild-to-moderate hereditary hearing loss in East Asian populations

Stop-gain mutation eliminating connexin 26 function; the most common GJB2 deafness allele in South Asian populations and the ancestral founder mutation carried into European Romani communities

The most common GJB2 deafness allele in the Ashkenazi Jewish population (~4% carrier frequency); frameshift deletion eliminates connexin 26 function and causes congenital sensorineural hearing loss in homozygotes or compound heterozygotes

Frameshift deletion eliminating connexin 26 function; the most common GJB2 deafness allele in East Asian populations causing severe-to-profound prelingual sensorineural hearing loss

Connexin 26 missense variant causing partial loss of cochlear gap junction function; the main mild-severity GJB2 deafness allele in European populations, with reduced penetrance and typically mild-to-moderate hearing loss

Near-gene variant tagging the TMPRSS3 hearing loss locus on chromosome 21, associated with susceptibility to sensorineural hearing loss and carrier status for DFNB8/10 deafness

Frameshift deletion in TMPRSS3 causing premature stop at codon 88; a severe pathogenic allele and Slovenian founder mutation causing DFNB8/10 autosomal recessive sensorineural hearing loss

Pathogenic missense variant at the TMPRSS3 autocatalytic cleavage site causing serine protease domain dysfunction and autosomal recessive sensorineural hearing loss (DFNB8/DFNB10); originally identified in consanguineous Turkish families

Hypomorphic missense variant in the TMPRSS3 serine protease catalytic domain; the most common TMPRSS3 pathogenic allele worldwide, causing DFNB8 progressive or DFNB10 congenital hearing loss depending on the second allele; a founder mutation in Korean, Chinese, Dutch, and German populations