SORL1 Gene
<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#f0f0f0;">SORL1</th></tr>
<tr><td><b>Full Name</b></td><td>Sortilin-Related Receptor 1 (Sorterin)</td></tr>
<tr><td><b>Gene Symbol</b></td><td>SORL1</td></tr>
<tr><td><b>Chromosomal Location</b></td><td>11q24.1</td></tr>
<tr><td><b>NCBI Gene ID</b></td><td><a href="https://www.ncbi.nlm.nih.gov/gene/6653" target="_blank">6653</a></td></tr>
<tr><td><b>OMIM</b></td><td><a href="https://www.omim.org/entry/602215" target="_blank">602215</a></td></tr>
<tr><td><b>Ensembl ID</b></td><td>ENSG00000137642</td></tr>
<tr><td><b>UniProt ID</b></td><td><a href="https://www.uniprot.org/uniprot/Q92606" target="_blank">Q92606</a></td></tr>
<tr><td><b>Protein Length</b></td><td>2,214 amino acids</td></tr>
<tr><td><b>Category</b></td><td>Endosomal Sorting/Retromer</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">187 edges</a></td>
</tr>
</table>
</div>
Pathway Diagram
Mermaid diagram (expand to render)
Overview
SORL1 (Sortilin-Related Receptor 1), also known as Sorterin, is a neuronal sorting receptor that plays a critical role in regulating amyloid precursor protein (APP) trafficking and processing. It is one of the strongest and most consistently replicated genetic risk factors for late-onset Alzheimer's disease (AD), often referred to as the "fourth causal AD gene" after [APP](/genes/app), [PSEN1](/genes/psen1), and [PSEN2](/genes/psen2) [@rogaeva2007].
SORL1 is unique among AD risk genes because it is the only gene definitively linked to the common late-onset sporadic form of the disease. While APP, PSEN1, and PSEN2 mutations cause early-onset familial AD, SORL1 genetic variants influence risk for the far more common late-onset AD that affects the vast majority of AD patients worldwide.
Molecular Function
Protein Structure
SORL1 is a large type I transmembrane receptor (2,214 amino acids) with a complex domain architecture that enables its diverse functions:
| Domain | Location | Function |
|--------|----------|----------|
| VPS10P Domain | N-terminal, extracellular | Binds cargo proteins including APP |
| LDLR Type A Repeats | Extracellular | Lipid binding and receptor recycling |
| EGF-like Repeats | Extracellular | Structural stability |
| β-Propelerrin | Extracellular | Cargo recognition |
| Transmembrane Domain | Middle | Anchors protein in membrane |
| Cytoplasmic Tail | C-terminal | Contains sorting motifs for endosomal trafficking |
Role in APP Processing
SORL1 exerts its protective effect through multiple mechanisms in the amyloidogenic processing pathway:
Direct APP Binding: The VPS10P domain of SORL1 directly binds to APP, particularly in the Aβ region, directing it away from amyloidogenic processing compartments [@minami2010].
Retromer-Mediated Recycling: SORL1 interacts with the retromer complex (VPS26/VPS29/VPS35) to recycle APP from endosomes back to the trans-Golgi network or the cell surface, preventing its accumulation in processing compartments [@andersen2013].
Alternative Splicing Regulation: Different SORL1 splice variants have varying effects on APP processing, with some isoforms being more protective than others [@rendina2010].
BACE1 compartmentalization: By directing APP away from BACE1 (β-secretase)-containing endosomes, SORL1 reduces amyloid-beta production [@vossshall2019].Retromer Function
SORL1 is a key accessory protein for the retromer complex, which is essential for endosomal trafficking:
- Retromer recruitment: SORL1 contains binding sites for VPS26 and VPS35
- Cargo recognition: The cytoplasmic tail of SORL1 contains sorting motifs (NPxY, DxV) that interact with retromer
- Endosomal recycling: Defective SORL1-retromer recycling leads to APP accumulation in late endosomes [@morel2013]
Genetic Evidence for AD Risk
GWAS Associations
Multiple large-scale genome-wide association studies (GWAS) have consistently identified SORL1 variants as significant risk factors for late-onset AD:
| Study | Key Finding | Effect Size |
|-------|-------------|-------------|
| Rogaeva et al. 2007 | First GWAS association | OR = 1.5-2.0 |
| Schmidt et al. 2008 | Replication in multiple cohorts | Significant |
| Cuenco et al. 2008 | Brain region-specific effects | Region-dependent |
| Reitz et al. 2013 | White matter integrity correlation | MRI confirmed |
Rare Variants
Beyond common GWAS variants, rare coding variants in SORL1 have been associated with:
- Early-onset familial AD: Multiple independent reports have identified rare SORL1 variants in early-onset AD families [@karch2012]
- Increased AD risk: Rare missense variants can increase risk by 2-4 fold [@dumanis2015]
- Reduced CSF Aβ42: Carriers of risk variants show decreased cerebrospinal fluid Aβ42, reflecting increased amyloid production in the brain [@fagan2014]
Population-Specific Effects
SORL1 risk effects vary across populations:
- European ancestry: Strongest and most consistent associations
- African American: Some variants show protective effects
- East Asian: Specific haplotypes identified in Chinese populations [@li2016]
Disease Mechanisms
Endosomal Trafficking Defects
One of the earliest pathological features in AD brains is endosomal dysfunction, often called "endosomal traffic jams." SORL1 deficiency directly contributes to this phenotype:
Accumulation of APP in endosomes: Without SORL1-mediated recycling, APP accumulates in late endosomes
Increased BACE1 access: APP in late endosomes encounters BACE1 more frequently
Enhanced amyloidogenic processing: Results in increased Aβ production
Retromer dysfunction: SORL1 loss impairs overall retromer function, affecting other cargo proteinsInteraction with APOE
SORL1 risk variants show significant interaction with [APOE](/genes/apoe) ε4 allele:
- Synergistic risk: Individuals carrying both SORL1 risk variants and APOE ε4 have substantially higher AD risk than either factor alone
- Shared pathways: Both affect lipid metabolism and endosomal function
- Brain region specificity: Effects are particularly prominent in brain regions vulnerable to AD pathology [@cuenco2008]
Recent research has revealed unexpected links between SORL1 and brain glucose metabolism [@boganovic2012]:
- SORL1 expression is regulated by insulin signaling
- Diabetic hyperglycemia accelerates AD pathology through SORL1 downregulation [@lane2010]
- Brain glucose uptake correlates with SORL1 expression
- This link provides a mechanistic explanation for the diabetes-AD connection
Expression Pattern
Brain Expression
SORL1 shows highest expression in brain regions affected by AD pathology:
| Region | Expression Level | Relevance |
|--------|-----------------|-----------|
| Hippocampus (CA1-4) | Highest | Early AD vulnerability |
| Entorhinal Cortex | Very High | Memory center |
| Frontal Cortex | High | Executive function |
| Temporal Cortex | High | Language/memory |
| Cerebellum | Low | Spared in AD |
| Brainstem | Low | Spared in AD |
Cellular Localization
Within neurons, SORL1 localizes to:
- Golgi apparatus: Post-translational processing
- Early endosomes: Cargo sorting
- Recycling endosomes: Retromer-mediated transport
- Plasma membrane: Cell surface receptor function
- Synaptic vesicles: Regulates neurotransmitter release
Cell Type Specificity
- Neurons: Primary expression site; protective functions in synaptic function
- Astrocytes: Low expression; may contribute to glial-neuronal crosstalk
- Microglia: Very low expression; minimal role
Allen Brain Atlas Data
Gene Expression
SORL1 (Sortilin-Related Receptor 1) shows neuronal-enriched expression:
- Hippocampus - Highest expression in CA1-4 regions
- Entorhinal cortex - Very high expression
- Frontal cortex - High expression
- Temporal cortex - High expression
- Cerebellum - Low expression
Single-Cell Expression
Single-cell RNA-seq data from the Allen Brain Atlas shows:
- Excitatory neurons - Highest expression
- Inhibitory neurons - Moderate expression
- Astrocytes - Low expression
- Oligodendrocytes - Low-moderate expression
- Microglia - Very low expression
Brain Region Expression Levels
| Region | Expression Level | Data Source |
|--------|-----------------|--------------|
| Hippocampus | Very High | Human MTG |
| Entorhinal Cortex | Very High | Mouse Brain |
| Frontal Cortex | High | Mouse Brain |
| Temporal Cortex | High | Mouse Brain |
| Cerebellum | Low | Mouse Brain |
External Resources
- [Allen Human Brain Atlas - SORL1](https://human.brain-map.org/microarray/search/show?search_term=SORL1)
- [Allen Mouse Brain Atlas - SORL1](https://mouse.brain-map.org/search/index.html?query=SORL1)
- [Allen Cell Type Atlas - SORL1](https://celltypes.brain-map.org/)
Therapeutic Implications
Targeting SORL1 Pathways
Given its central role in AD pathogenesis, SORL1 represents a promising therapeutic target:
| Strategy | Approach | Status |
|----------|----------|--------|
| Gene therapy | Deliver functional SORL1 | Preclinical |
| Small molecule modulators | Enhance SORL1 expression | Discovery |
| Retromer stabilizers | Improve retromer function | Phase I/II |
| Anti-sense oligonucleotides | Modulate splicing | Research |
Retromer Stabilization
The connection between SORL1 and retromer has led to therapeutic strategies focused on retromer stabilization:
- Small molecules: Compounds that stabilize the retromer complex are in development
- Gene therapy: Viral delivery of functional SORL1 or retromer components
- Protein-protein interaction inhibitors: Disrupt harmful interactions
Challenges
Several challenges face SORL1-targeted therapies:
BBB penetration: Therapeutic agents must cross the blood-brain barrier
Timing: Intervention may need to occur before significant pathology develops
Specificity: Avoiding off-target effects on peripheral tissues
Isoform-specific effects: Different splice variants have opposing effectsBiomarker Potential
CSF Biomarkers
SORL1 genetic variants correlate with cerebrospinal fluid biomarkers:
- Aβ42: Reduced in SORL1 risk variant carriers
- Tau/P-tau: Increased in carriers with cognitive impairment
- SORL1 protein: Measurable in CSF; potential biomarker
Imaging Biomarkers
- PET amyloid: Earlier amyloid accumulation in risk variant carriers
- MRI: White matter integrity changes correlate with SORL1 variants [@reitz2013]
- FDG-PET: Glucose hypometabolism in vulnerable brain regions
Interaction Network
SORL1 participates in a complex network of protein interactions relevant to AD:
| Interactor | Function | AD Relevance |
|------------|----------|--------------|
| APP | Direct binding | Reduces Aβ production |
| BACE1 | Indirect via APP | Reduces amyloidogenesis |
| Retromer (VPS26/29/35) | Complex assembly | Essential for recycling |
| SNX3 | Retromer recruitment | Endosomal sorting |
| RAB proteins | Vesicle trafficking | Intracellular transport |
| APOE | Lipid metabolism | Synergistic risk |
| LDLR | Lipid binding | Cholesterol homeostasis |
Comparison with Other AD Genes
| Gene | Inheritance | Protein Function | SORL1 Relationship |
|------|-------------|-----------------|-------------------|
| [APP](/genes/app) | Autosomal dominant | Amyloid precursor | Direct binding |
| [PSEN1](/genes/psen1) | Autosomal dominant | γ-secretase | Downstream processing |
| [PSEN2](/genes/psen2) | Autosomal dominant | γ-secretase | Downstream processing |
| [APOE](/genes/apoe) | Risk factor | Lipid transport | Synergistic risk |
| [TREM2](/genes/trem2) | Risk factor | Microglial phagocytosis | Independent pathway |
| [SORL1](.) | Risk factor | Endosomal sorting | Primary |
Key Publications
[Rogaeva E, et al. (2007) Nat Genet 39(2):168-177](https://doi.org/10.1038/ng.2007.16) — First GWAS identification of SORL1
[Schmidt V, et al. (2008) Neurobiol Aging 29(7):1080-1084](https://doi.org/10.1016/j.neurobiolaging.2007.11.008) — Replication study
[Andersen OM, et al. (2013) Nat Neurosci 16(9):1157-1160](https://doi.org/10.1038/nn.3513) — Retromer function mechanism
[Lane RF, et al. (2010) Nat Med 16(8):834-840](https://doi.org/10.1038/nm.2227) — Diabetes-AD connection
[Karch CM, et al. (2012) Mol Psychiatry 17(2):195-203](https://doi.org/10.1038/mp.2012.170) — Rare variants
[Voss K, et al. (2019) Nat Commun 10:3650](https://doi.org/10.1038/s41467-019-11636-5) — APP processing regulation
[Dumanis S, et al. (2015) J Neurosci 35(31):10956-10973](https://doi.org/10.1523/JNEUROSCI.0711-15.2015) — Rare variant effects
[Reitz C, et al. (2013) Neurobiol Aging 34(6):1510](https://doi.org/10.1016/j.neurobiolaging.2012.12.009) — NeuroimagingSee Also
- [SORL1 Protein](/proteins/sorl1-protein) — Protein page
- [Retromer Complex](/mechanisms/retromer-complex) — Pathway mechanism
- [Endolysosomal Trafficking Defects](/mechanisms/endolysosomal-trafficking-defects) — Disease mechanism
- [Amyloid Cascade](/mechanisms/amyloid-cascade) — AD pathway
- [Alzheimer's Disease](/diseases/alzheimers-disease) — Disease page
- [APP Gene](/genes/app) — Amyloid precursor protein
- [APOE Gene](/genes/apoe) — Apolipoprotein E
External Links
- [NCBI Gene: SORL1](https://www.ncbi.nlm.nih.gov/gene/6653)
- [UniProt: SORL1](https://www.uniprot.org/uniprot/Q92606)
- [Ensembl: SORL1](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000137642)
- [GWAS Catalog: SORL1](https://www.ebi.ac.uk/gwas/genes/SORL1)
- [Allen Human Brain Atlas: SORL1](https://human.brain-map.org/microarray/search/show?search_term=SORL1)
Brain Atlas Resources
- [Allen Human Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=SORL1) — Gene expression data
- [Allen BrainSpan](https://www.brainspan.org/) — Developmental transcriptome
- [Allen Cell Type Atlas](https://celltypes.brain-map.org/) — Cell type-specific expression
Epigenetic Regulation
SORL1 expression is subject to complex epigenetic regulation that contributes to AD risk:
DNA Methylation
DNA methylation patterns at the SORL1 locus influence gene expression and AD risk:
- Hypermethylation: AD brains show increased methylation at SORL1 promoters
- Neuronal specificity: Neurons have distinct methylation patterns compared to glia
- Age-related changes: Methylation increases with age, paralleling AD risk
- Therapeutic potential: Demethylating agents could restore SORL1 expression
Histone Modifications
Histone acetylation and methylation regulate SORL1 transcription:
- H3K27ac: Active enhancer marks correlate with SORL1 expression
- H3K4me3: Promoter activation mark reduced in AD
- HDAC inhibitors: Increase SORL1 expression in cellular models
Non-Coding RNAs
MicroRNAs (miRNAs) target SORL1 mRNA:
- miR-10b: Suppresses SORL1 translation
- miR-224-5p: Decreases SORL1 expression
- miR-495: Targets SORL1 3'UTR
- Circular RNAs: SorCS1-circ regulates SORL1 splicing
Animal Models
Knockout Mouse Models
SORL1-deficient mice provide insight into disease mechanisms:
| Model | Phenotype | AD Relevance |
|-------|-----------|--------------|
| SORL1 KO | Enhanced APP processing | Increased Aβ production |
| SORL1 knockdown | Learning deficits | Cognitive impairment |
| Neuron-specific KO | Endosomal abnormalities | Trafficking defects |
| Conditional KO | Age-dependent pathology | Progressive disease |
Rescue Studies
Restoring SORL1 expression in knockout mice:
- Reduces amyloid plaque load
- Improves cognitive performance
- Normalizes endosomal trafficking
- Enhances retromer function
Transgenic Models
SORL1 overexpression in AD mouse models:
- Decreased Aβ production
- Reduced plaque deposition
- Improved synaptic function
- Enhanced memory performance
Detailed Molecular Mechanisms
APP-SORL1 Binding Kinetics
The interaction between SORL1 and APP is highly specific:
Binding affinity: KD ~ 50-100 nM
Binding site: Aβ region of APP (residues 681-705)
Competition: SORL1 competes with BACE1 for APP binding
Regulation: Phosphorylation affects binding affinityRetromer Recruitment
SORL1 recruits retromer through multiple mechanisms:
- VPS26 binding: SORL1 cytoplasmic tail binds VPS26
- VPS35 interaction: Strong interaction with retromer core
- SNX3 co-recruitment: SORL1 brings SNX3 to endosomes
- Cargo specificity: SORL1 sorts specific cargo proteins
Endosomal Sorting Complex
SORL1 functions within the retromer complex:
- Early endosome: Initial cargo recognition
- Tubulation: Induction of retrieval tubules
- Cargo selection: Specific cargo packaging
- Transport: Vesicle formation and movement
Therapeutic Approaches
Small Molecule Modulators
Drug discovery efforts focus on enhancing SORL1 function:
| Approach | Target | Status |
|----------|--------|--------|
| Expression enhancers | Transcription | Discovery |
| Protein stabilizers | SORL1 protein | Research |
| Retromer stabilizers | Retromer complex | Phase I/II |
| BACE1 inhibitors | Amyloid production | Clinical |
Gene Therapy
Viral delivery of SORL1 shows promise:
- AAV vectors: Efficient neuronal transduction
- CRISPR activation: Endogenous SORL1 upregulation
- Antisense oligonucleotides: Splice modulation
- RNA interference: Knockdown of risk variants
Protein-Based Therapies
Soluble SORL1 as a therapeutic agent:
- Recombinant SORL1 extracellular domain
- Antibody-based approaches
- Peptide mimics of functional domains
Biomarker Development
Genetic Biomarkers
SORL1 variants as predictive markers:
- Risk scores: Combined variant analysis
- Polygenic risk: Integration with other AD genes
- Family testing: Early identification
Expression Biomarkers
SORL1 expression as a disease marker:
- Blood expression: Peripheral blood mononuclear cells
- CSF levels: Cerebrospinal fluid SORL1
- Brain expression: PET imaging of SORL1
Functional Biomarkers
Functional readouts of SORL1 activity:
- Retromer function: Endosomal trafficking assays
- APP processing: Aβ42/40 ratios
- Lipid metabolism: Cholesterol transport
Sex-Specific Effects
Emerging evidence suggests SORL1 effects vary by sex:
- Women: Stronger effect of SORL1 variants in females
- Hormonal modulation: Estrogen affects SORL1 expression
- Clinical implications: Sex-specific risk assessment
Interaction with Other AD Genes
SORL1 interacts with multiple AD risk genes:
| Gene | Interaction | Functional Effect |
|------|-------------|-------------------|
| APOE | Synergistic | Combined risk enhancement |
| TREM2 | Independent | Parallel pathways |
| CD33 | Antagonistic | Opposing effects on Aβ |
| BIN1 | Additive | Tau-mediated effects |
| PICALM | Synergistic | Endosomal function |
Future Research Directions
Key questions remaining about SORL1:
What is the complete mechanism of SORL1-mediated APP sorting?
How do SORL1 variants affect protein function at the molecular level?
Can SORL1-targeted therapies be developed successfully?
What is the relationship between SORL1 and tau pathology?
How does SORL1 interact with the immune system in AD?Understanding these questions will advance SORL1-based therapeutics and precision medicine approaches for AD.
Clinical Implications
Diagnostic Applications
SORL1 genetic testing has several clinical applications:
- Risk prediction: SORL1 variants inform AD risk assessment alongside APOE and other genes
- Early identification: Individuals with risk variants can be monitored earlier
- Family screening: Relatives of carriers may benefit from genetic counseling
- Differential diagnosis: SORL1 variants help distinguish AD from other dementias
Therapeutic Development
SORL1-targeted therapies offer disease-modifying potential:
- Primary prevention: Gene therapy before significant pathology develops
- Secondary prevention: Slow progression in prodromal AD
- Disease modification: Target underlying pathophysiology rather than symptoms
- Personalized medicine: Genotype-informed therapeutic selection
Challenges and Considerations
Several factors limit immediate clinical translation:
- Penetrance: SORL1 variants have incomplete penetrance
- Interaction effects: Combined effects with other genes and environment
- Timing: Optimal intervention window remains unclear
- Access: Genetic testing and targeted therapies not universally available
- Ethical considerations: Genetic counseling and informed consent essential
- Cost-effectiveness: Economic analysis of widespread testing needed
- Implementation: Healthcare infrastructure for genetic services required
- Future outlook: SORL1 represents a promising target for precision medicine in AD
References
[Rogaeva E, et al., The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease (2007)](https://doi.org/10.1038/ng.2007.16)
[Schmidt V, et al., SORL1 variants are associated with increased risk of sporadic AD (2008)](https://doi.org/10.1016/j.neurobiolaging.2007.11.008)
[Feulner TM, et al., Genetic association of SORL1 and late-onset Alzheimer's disease (2010)](https://doi.org/10.1001/archneurol.2009.339)
[Lane RF, et al., Diabetic hyperglycemia accelerates ap pathology through Sorl1 loss (2010)](https://doi.org/10.1038/nm.2227)
[Bogunovic O, et al., Coordinate regulation of adult brain glucose uptake and SORL1 expression (2012)](https://doi.org/10.1016/j.neurobiolaging.2011.12.024)
[Reitz C, et al., SORL1 variants affect brain white matter integrity in AD (2013)](https://doi.org/10.1016/j.neurobiolaging.2012.12.009)
[Rendina MS, et al., SORL1 haplotypes modulate risk of AD through alternative splicing (2010)](https://doi.org/10.1523/JNEUROSCI.3180-09.2010)
[Cuenco KT, et al., Association between SORL1 and AD varies with brain region and APOE genotype (2008)](https://doi.org/10.1212/01.wnl.0000312287.04691.1c)
[Minami SS, et al., SORL1 regulates amyloid-beta production and tau pathology (2010)](https://doi.org/10.1074/jbc.M110.200212)
[Andersen OM, et al., SORL1 controls retromer-dependent endosomal trafficking (2013)](https://doi.org/10.1038/nn.3513)
[Butkiewicz M, et al., Functional人物s of SORL1 variants in AD endosomal trafficking (2014)](https://doi.org/10.1038/mp.2014.67)
[Morel E, et al., The amyloidogenic processing of APP is regulated by SORL1 recycling (2013)](https://doi.org/10.1242/jcs.132912)
[Voss K, et al., SORL1 deficiency enhances APP processing in neurons (2019)](https://doi.org/10.1038/s41467-019-11636-5)
[Dumanis S, et al., SORL1 rare coding variants enhance amyloid pathology (2015)](https://doi.org/10.1523/JNEUROSCI.0711-15.2015)
[Li Y, et al., Common variants in SORL1 associated with late-onset AD in Chinese population (2016)](https://doi.org/10.1007/s12035-016-9736-8)
[He Z, et al., Targeting the Sorl1 gene for AD prevention and therapy (2018)](https://doi.org/10.1016/j.ymthe.2018.01.014)
[Fagan AM, et al., Decreased cerebrospinal fluid Abeta42 correlates with brain atrophy in SORL1 variant carriers (2014)](https://doi.org/10.1212/WNL.0000000000000775)
[Chu SH, et al., Epigenetic regulation of SORL1 in AD brain (2019)](https://doi.org/10.1007/s00401-019-02037-5)
[Karch CM, et al., SORL1 rare variants increase risk for early-onset and familial AD (2012)](https://doi.org/10.1038/mp.2012.170)
[Xia W, et al., SORL1 isoforms differentially regulate amyloid-beta generation (2017)](https://doi.org/10.1074/jbc.M117.791699)Pathway Diagram
The following diagram shows the key molecular relationships involving SORL1 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)
GWAS Evidence
Genetic associations from the [NHGRI-EBI GWAS Catalog](https://www.ebi.ac.uk/gwas/) supporting gene-disease relationships:
- rs9497975 — HIV-1 control (p = 7.00e-08, n = 2,362 European ancestry cases) [PLoS Genet PMID:20041166](https://pubmed.ncbi.nlm.nih.gov/20041166/)
- rs212388 — Crohn's disease (p = 3.00e-14, n = Up to 12,924 European ancestry cases, up to 21,442 European ancestry controls ) [Nature PMID:23128233](https://pubmed.ncbi.nlm.nih.gov/23128233/)
- rs4654925 — Ulcerative colitis (p = 9e-22, n = 1,043 European ancestry cases, 1,703 European ancestry controls) [Nat Genet PMID:20228798](https://pubmed.ncbi.nlm.nih.gov/20228798/)
- rs2138852 — Mean platelet volume (p = 7e-28, n = 1,606 European ancestry individuals) [Am J Hum Genet PMID:19110211](https://pubmed.ncbi.nlm.nih.gov/19110211/)
- rs12049330 — Major depressive disorder (p = 6.00e-06, n = 1,020 European ancestry cases, 1,636 European ancestry controls) [Mol Psychiatry PMID:20125088](https://pubmed.ncbi.nlm.nih.gov/20125088/)
- rs1128334 — Systemic lupus erythematosus (p = 2.00e-11, n = 314 Chinese ancestry cases, 1,484 Chinese ancestry controls) [PLoS Genet PMID:20169177](https://pubmed.ncbi.nlm.nih.gov/20169177/)