Schizophrenia

From SNPedia

wikipedia:schizophrenia is a good place to learn about the disease.

Mother vs child genetics affects the risk of schizophrenia [1]

[2] Schizophrenia is widely held to stem from the combined effects of multiple common polymorphisms, each with a small impact on disease risk. We suggest an alternative view: that schizophrenia is highly heterogeneous genetically and that many predisposing mutations are highly penetrant and individually rare, even specific to single cases or families. This `common disease – rare alleles' hypothesis is supported by recent findings in human genomics and by allelic and locus heterogeneity for other complex traits.

All of these SNPs have been linked to schizophrenia

1. rs10790212
2. rs11743803
3. rs165599
4. rs175174
5. rs1800532
6. rs211105
7. rs310762
8. rs3738401
9. rs4680
10. rs4938445
11. rs4950928
12. rs497768
13. rs6675281
14. rs707284
15. rs7598440
16. rs7933505
17. rs795009
18. rs839523
19. rs947267
20. rs27388, in the [MEGF10]] gene
21. rs2270641, in the SLC18A1 gene
22. rs17101921, on ch 10q25-26

A recent (2007) whole genome association study identified several SNPs as significantly associated with schizophrenia, all located in the pseudoautosomal region of the X and Y chromosomes (Xp22.32/Yp11.3) [PMID 17522711]:

• rs4129148, near the CSF2RA gene
• rs28694718 and rs28414810, part of a haplotype block in intron 8 of the CSF2RA gene
• rs6422441, rs6603272, and rs17883192, all part of a haplotype block spanning introns 4, 5 and 6 of the IL3RA gene

Several meta-analyses have implicated one or more SNPs in the dopamine D2 receptor DRD2 gene as a risk factor, such as:

• rs1801028
• rs6277

Another form of genetic variation is known as "runs of homozygosity" (ROH), whereby for relatively long stretches of a person's genome both chromosomes are identical. Nine specific regions have tentatively been found [PMID 18077426] to show ROHs to a greater degree in schizophrenics; the core SNPs from each of these regions are:

• rs11225703, on chromosome 11
• rs2848745, on chromosome 18
• rs17651507, on chromosome 17
• rs2437896, on chromosome 2
• rs2499846, on chromosome 1
• rs4958803, on chromosome 5
• rs2053149, on chromosome 14
• rs7582658, on chromosome 2
• rs2119783, on chromosome 8

Another theory attributes schizophrenia to an accumulation of multiple, individually rare mutations (i.e. not common SNPs) that alter genes in neurodevelopmental pathways. This was primarily based on a study of microdeletions and microduplications of size >100 kb that were identified by microarray comparative genomic hybridization of genomic DNA from 150 individuals with schizophrenia.[PMID 18369103]

There have also been numerous studies finding no statistically valid association between any single SNP and schizophrenia. For example: in a large genetic association study of 14 schizophrenia candidate genes (RGS4, DISC1, DTNBP1, STX7, TAAR6, PPP3CC, NRG1, DRD2, HTR2A, DAOA, AKT1, CHRNA7, COMT, and ARVCF) and 1,870 Caucasian patients, no SNPs were found to be statistically meaningful, and even the four functional polymorphisms in COMT, DRD2, and HTR2A showed no association. This study did not rule over small effects from these SNPs however.[PMID 18198266]

Some SNPs have also been reported to be associated with better treatment outcome:

• rs6280, correlated to better response to olanzapine

thinkgene CNVs at 22q11.2 may account for 15% of sporadic cases.