rs11931074 — SNCA

SNCA 3′-region variant consistently associated with Parkinson's disease risk across Asian and European populations

See your personal result for SNCA

Upload your DNA data to find out which genotype you carry and what it means for you.

Upload your DNA data

Works with 23andMe, AncestryDNA, and other DNA test exports. Results in under 60 seconds.

The SNCA gene11 SNCA gene
Alpha-synuclein (SNCA) encodes the protein that forms the pathological hallmark of Parkinson's disease — Lewy bodies and Lewy neurites — in dopaminergic neurons of the substantia nigra harbours multiple independent risk variants spread across its genomic structure. rs11931074 sits in the 3′ downstream region of SNCA.

rs11931074 has been studied across more published meta-analyses than virtually any other common SNCA variant and emerges in the most recent 2025 systematic review as the single most robust SNCA risk marker — showing consistent, low-heterogeneity associations with Parkinson's disease across all tested genetic models and in both Asian and European populations. Its independence from the 3′-block variant rs356219 (which operates through a different regulatory mechanism in a partially overlapping region) makes it an additive source of risk information at the SNCA locus.

The Mechanism

The TT genotype has been directly associated with significantly higher alpha-synuclein protein levels in human brain tissue.

The downstream consequence mirrors the rs356219 story: chronically elevated alpha-synuclein increases the probability of misfolding, oligomerization, and seeding of the insoluble fibrillar aggregates that destroy dopaminergic neurons in the substantia nigra and trigger the progressive motor and non-motor symptoms of Parkinson's disease.

The Evidence

The largest meta-analysis22 The largest meta-analysis
Liu et al. An updated analysis with 45,078 subjects confirms the association between SNCA rs11931074 and Parkinson's disease. Neurological Sciences, 2018 pooled 33 studies involving 15,368 PD patients and 29,710 controls. Every tested genetic model reached significance: allelic OR 1.36 (95% CI 1.31–1.42); homozygous TT vs. GG OR 1.87 (95% CI 1.68–2.09); recessive OR 1.58 (95% CI 1.46–1.72). Crucially, significant associations appeared in both Asian and Caucasian subgroups, confirming that the risk signal is not ethnicity-specific.

A 2020 meta-analysis33 A 2020 meta-analysis
Du et al. Association between alpha-synuclein (SNCA) rs11931074 variability and susceptibility to Parkinson's disease: an updated meta-analysis of 41,811 patients. Neurological Sciences, 2020 (13,403 cases, 28,408 controls) confirmed these results with allelic OR 1.28 (95% CI 1.12–1.45; p=0.0001) and recessive OR 1.40 (95% CI 1.18–1.68; p=0.0002). The study specifically noted low heterogeneity across studies and no evidence of publication bias — two hallmarks of a genuine, reproducible association rather than an artefact of selective reporting.

The 2025 systematic review and meta-analysis44 The 2025 systematic review and meta-analysis
Mohammadi et al. Common SNCA Genetic Variants and Parkinson's Disease Risk. International Journal of Molecular Sciences, 2025 including 27 studies explicitly identified rs11931074 as showing "consistent associations with PD across all models" and confirmed it as the most robust common SNCA PD risk variant.

Beyond disease susceptibility, rs11931074 shows associations with PD clinical features. A 2015 Chinese cohort study55 A 2015 Chinese cohort study
Chen et al. Hyposmia correlates with SNCA variant and non-motor symptoms in Chinese patients with Parkinson's disease. Parkinsonism & Related Disorders, 2015 (218 PD patients) found the TT genotype conferred OR 3.24 (95% CI 1.23–8.51) for hyposmia — reduced sense of smell — a well-recognized early non-motor marker of PD. The same study confirmed TT genotype was associated with significantly higher alpha-synuclein levels in brain tissue (p=0.0082), providing the mechanistic link between genotype and phenotype.

A 2019 resting-state fMRI study66 2019 resting-state fMRI study
SNCA rs11931074 polymorphism correlates with spontaneous brain activity and motor symptoms in Chinese patients with Parkinson's disease. Journal of Neural Transmission, 2019 found that TT carriers showed altered spontaneous brain activity in the right angular gyrus compared to GT/GG carriers, with ALFF values negatively correlated with UPDRS III motor scores — suggesting the variant modulates the neural circuitry underlying motor control in affected patients.

Practical Actions

The functional consequence of rs11931074 T-allele carriage — higher alpha-synuclein expression — is the same biological target as for rs356219, meaning the protective strategies that address elevated SNCA expression apply here too: supporting mitochondrial function against alpha-synuclein-driven complex I dysfunction, promoting autophagy to clear misfolded protein, and reducing environmental exposures that independently upregulate SNCA.

The clinically important addition from rs11931074 research is the hyposmia connection. Loss of smell is one of the earliest detectable markers of Parkinson's pathology, appearing years before motor symptoms. TT carriers who notice a declining sense of smell should discuss this with their doctor as a potential early indicator warranting neurological evaluation — the combination of genotype and symptom substantially elevates clinical concern.

Because T allele frequency differs dramatically between populations (about 7% in Europeans versus 53% in East Asians), the genotype interpretation varies substantially by ancestry: TT homozygosity is rare in Europeans (about 1%) but relatively common in East Asians (about 28%), meaning the recessive risk signal has very different population-level impact.

Interactions

rs11931074 and rs356219 are both located in the 3′ region of the SNCA locus but are in different linkage disequilibrium blocks. Independent carriage of risk alleles at both loci may compound alpha-synuclein overproduction through additive regulatory effects, though no single study has formally quantified the joint genotype effect.

rs356182, an intronic SNCA variant affecting neuronal differentiation, represents a third independent risk signal at the SNCA locus. Carriers of risk alleles at rs11931074, rs356219, and rs356182 simultaneously may face substantially elevated cumulative PD susceptibility through three distinct mechanisms — disease risk, elevated expression, and impaired neuronal differentiation — though this triple-carrier scenario has not been formally studied.

Genotype Interpretations

What each possible genotype means for this variant.

GG Standard Expression Normal

Normal SNCA 3′ UTR function with population-average Parkinson's risk

You carry two copies of the G allele at rs11931074, which is the common form in European populations (approximately 86% of Europeans are GG). This genotype is not associated with elevated alpha-synuclein levels through this variant and carries population-average risk for Parkinson's disease.

GT Elevated Expression Risk Intermediate

One T copy modestly increases SNCA expression and Parkinson's disease risk

Pay particular attention to any changes in your sense of smell. Research in Chinese PD patients found that TT homozygotes have more than 3-fold increased risk of hyposmia among PD patients; while GT heterozygotes carry a lower risk than TT, the same biological mechanism applies. Progressive smell loss, in combination with your genotype, would warrant discussion with a neurologist.

TT High Expression Risk High Risk

Two T copies elevate SNCA expression, significantly increasing Parkinson's risk and non-motor symptom burden

The TT genotype represents the peak of this variant's dose-response gradient: each T allele incrementally raises SNCA protein output, and two T alleles produce the highest expression level. This elevated baseline increases the probability of alpha-synuclein misfolding, oligomer formation, and ultimately the Lewy body pathology that destroys dopaminergic neurons in the substantia nigra.

The non-motor features associated with TT deserve particular attention. Hyposmia — reduced ability to detect or identify smells — is one of the earliest detectable markers of Parkinson's pathology, often preceding motor symptoms by years. The 2015 Chinese cohort found TT carriers with PD had OR 3.24 for hyposmia (p=0.017), and the same study directly measured higher alpha-synuclein in TT brain tissue (p=0.0082), establishing the mechanistic link.

A 2019 fMRI study found TT carriers had elevated spontaneous neural activity in the right angular gyrus — a region involved in multi-sensory integration and attention — compared to GT/GG carriers, with these values inversely correlated with motor symptom severity (UPDRS III). This suggests that even at the neural circuit level, TT genotype produces measurable alterations in brain organization.

The 2025 meta-analysis singled out rs11931074 as the most consistent SNCA risk marker across all genetic models and all populations studied.