{{Rsnum
|rsid=2535629
|Gene=ITIH3
|Chromosome=3
|position=52799203
|Orientation=minus
|GMAF=0.4867
|Gene_s=ITIH3
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(C;C)
|geno2=(C;T)
|geno3=(T;T)
}}{{ population diversity
| geno1=(C;C)
| geno2=(C;T)
| geno3=(T;T)
| CEU | 51.3 | 40.7 | 8.0
| HCB | 28.5 | 54.7 | 16.8
| JPT | 31.9 | 48.7 | 19.5
| YRI | 4.8 | 32.0 | 63.3
| ASW | 8.8 | 43.9 | 47.4
| CHB | 28.5 | 54.7 | 16.8
| CHD | 38.5 | 47.7 | 13.8
| GIH | 35.6 | 41.6 | 22.8
| LWK | 8.2 | 45.5 | 46.4
| MEX | 19.0 | 43.1 | 37.9
| MKK | 21.8 | 55.8 | 22.4
| TSI | 24.5 | 53.9 | 21.6
| HapMapRevision=28
}}The SNP is located in an intron of ''ITIH3'', a domain of a protease inhibitor. [[rs2535629]] was recently shown to be significantly associated with multiple mental disorders: [[autism]]-spectrum disorders, [[attention deficit hyperactivity disorder]], [[bipolar disorder]], [[depression]], and [[schizophrenia]], where A is the risk allele. {{PMID|23453885|OA=1
}} However, the causative gene has not yet been determined since the SNP is in linkage disequilibrium with more than 30 genes in the surrounding 1Mb region.

===Symptom-based diagnosis===
Mental disorders are currently classified based on symptoms and the course of the disease, as specified by the Diagnostic and Statistical Manual of Mental Disorders (DSM). However, presentation of diseases as classified by DSM is highly heterogeneous. As genomic data is becoming more abundant, the possibility of diagnosis based on the underlying molecular cause is being discussed.

===Familial mental disorders===
It has long been known that relatives of mental health patients have a higher chance of having a psychiatric illness, but not necessarily the same illness as the patient. {{PMID|4015321}}  {{PMID|22474230}} [http://link.springer.com/article/10.1007%2FBF02279760#page-1] This has led to the idea that common genetic factors underlie multiple psychiatric disorders. A GWAS carried out by Smoller ''et al'' identified three SNPs predictive of autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia – [[rs2535629]], [[rs11191454]], and [[rs2799573]] – and one predictive of bipolar disorder and schizophrenia only – [[rs1024582]]. 

===Implicating study===
The study analyzed 33332 cases and 27888 controls, where patients were of European descent and met criteria from DSM-III revised or DSM-IV. {{PMID|23453885|OA=1
}} 1,250,922 autosomal SNPs were examined.
The study divided patients and controls into five groups:
* Autism-spectrum disorders (4788 trio cases (two parents and an affected offspring who inherited the allele in question), 4788 trio pseudocontrols (two parents and an offspring who did not inherit the allele in question), 161 cases and 526 controls);
* Attention deficit-hyperactivity disorder (1947 trio cases, 1947 trio pseudocontrols, 840 cases, 688 controls);
* Bipolar disorder (6990 cases, 4820 controls);
* Major depressive disorder (9227 cases, 7383 controls);
* Schizophrenia (9379 cases, 7736 controls)
[[rs2535629]] has been shown to be predictive of the five disorders above with a combined odds ratio 1.10, p-value 2.54*10<sup>-12</sup>. For a complex disorder like any of the five illnesses above, odds ratio of 1.10 suggests an important genetic locus, while the p-value above indicates strong confidence in the result.

===Corroborating Studies===
====Bipolar Disorder====
A study by the Scott ''et al'' identified [[rs1042779]] as a predictor of bipolar disorder. {{PMID|19416921|OA=1
}} [[rs1042779]] is 12kb away from [[rs2535629]], but within the [[rs2535629]] 1Mb haplotype. The odds ratio of [[rs1042779]] was 1.19, with p-value 1.8*10<sup>-7</sup>. The study included 3944 patients with bipolar disorder I and II diagnosed based on DSM-III or DSM-IV and 14507 controls. All subjects were of European ancestry.

====Major Depressive and Bipolar Disorder====
Another study identified [[rs2251219]], a SNP 248kb away from [[rs2535629]], but within the 1Mb haplotype, as significantly associated with bipolar disorder and combined major depressive disorder. {{PMID|20081856|OA=1
}} The SNP was found to have an odds ratio of 0.87 with p-value 3.63*10<sup>-8</sup>. The study analyzed individuals of European origin, of whom 8765 cases of bipolar disorder and major depressive disorder as defined by DSM-IV and 9122 controls.

{{PMID Auto
|PMID=22472876
|Title=A mega-analysis of genome-wide association studies for major depressive disorder.
|OA=1
}}

{{on chip | Affy GenomeWide 6}}