This will be the first in a series of articles providing lists of various genes that have been proven to correlate with specific mental disorders, or at least suspected of being correlated with them.
–MCH (Major histocompatibility complex) (Elsevier, 2012) – Researchers believe that a part of the genome instrumental in proper immune system functioning is correlated with susceptibility to schizophrenia. Study of MCH genes among 13,195 schizophrenic patients suggests that there are alleles at the MHC locus which contribute to determining whether or not one develops the disease. The immune system has long been believed to be correlated with the development of schizophrenia, particularly elements such as gluten sensitivity, viral infections, and alterations in the blood’s cytokine levels and cerebrospinal fluid (Elsevier, 2012).
–SETDIA (Columbia University Medical Center, 2014) – Researchers in this study say that the number and nature of mutations is instrumental in mediating schizophrenic symptoms, rather than a single, isolable mutation. Having studied 231 schizophrenic subjects, they believe that the disease results from damage done to several genes. It both increases the likelihood of exhibiting these symptoms, as well as contributing to the severity of the symptoms.
Two mutations in SETD1A were particularly correlated with schizophrenia. The gene helps mediate chromatin modification. “Chromatin is the molecular apparatus that packages DNA into a smaller volume so it can fit into the cell and physically regulate how genes are expressed. Chromatin modification is therefore a crucial cellular activity”(Columbia University Medical Center, 2014). Researchers believe that damage to this gene is related to severeal neurodevelopmental and psychiatric problems. The researchers say that chromatin regulation was the most common denominator in various studies on the genesis of schizophrenia.
–LINE-1 – Retrotransposons, also known as “junk DNA,” have been suggested as a possible culprit in schizophrenia. LINE-1 (Long Interspersed Nuclear Elements) are much more present in the brains of schizophrenics, the researchers say, than those of controls. The scientists also say that this DNA alters the expression of genes that are correlated with schizophrenic symptoms during the development of the brain.
These particular retrotransposons are already suspected of a number of serious health problems, such as cancer. Both genetic and environmental factors, the researchers argue, can lead to the increase of this DNA in neurons. They also argue that inserting LINE-1 into genes that are implicated in the function of synapses or related to schizophrenia may disrupt ordinary function of the brain.
–Chromosome 17 (Cell Press, 2010) – 24 of 23,000 patients with autism-spectrum disorder were found to have a deletion on this chromosome (17q12 deletion). The copy-number variation was remarkably absent in all of thet 52,448 controls. This makes the deletion statistically significant.Those with the deletion, the researchers say, are, by this measurement, 13.58 more likely to develop ASD or schizophrenia.
–CACNA1B (Children’s Hospital of Phildelphia, 2010) – This gene carries codes for proteins which utilize calcium signals. These calcium signals contribute to determining how neurotransmitters are released in the brain. Copy number variations (CNVs) are associated with this gene in schizophrenia.
–DOC2A (Children’s Hospital of Philadelphia, 2010) – Serves a function similar to the above. Copy number variations (CNVs) are associated with this gene in schizophrenia.
-Chromosome 16 – (Children’s Hospital of Philadelphia, 2010) Deletions in a specific region of this gene are associated with autism, but they have also been found to be associated with schizophrenia.
–OLIG2 (The Mount Sinai Hospital, 2006) – Researchers have found that OLIG2, short for oligodendrocyte lineage transcription factor 2, regulates myelin, which is itself formed by oligodendrocytes; a kind of central nervous system cell. Some researchers have suggested that schizophrenia involves changes in myelin, the fatty substance, known as “white matter”, in the brain. This white matter coats nerve fibers and is very important for the proper functioning of the brain. Researchers do know that schizophrenia have inadequate levels of oligodendrocytes, but the reason for this is unclear.
The genetic information of 673 schizophrenic patients were compared with 716 non-schizophrenic patients. Genetic variation in OLIG2 was indeed highly correlated with schizophrenia. The co-ordinate expression of OLIG2 with CNP and ERBB4, which are also important in the development of myelin, was also highly correlated with schizophrenia, suggesting that disorders of myelin may involved groups of genes rather than single genes.
–TOP3B (Wellcome Trust Sanger Institute, 2013) – associated with schizophrenia, autism and intellectual impairment. This gene may partially explain the tendenecy of schizophrenia to be paired with cognitive dysfunction. The study was conducted among the Finnish, who have a schizophrenia frequency 3x those of other countries. Highly unusual genetic deletions which affect TOP3B among Northeastern Finnish populations seem to increase the susceptibility of the population to schizophrenia 2-fold. The researchers believe that this deletion is responsible for the tendency of Finnish people to be more likely to suffer from schizophrenia and learning disorders.
The gene is responsible for encoding a protein that helps cells unwind and wind DNA helices. Rather than DNA, it acts on mRNA. It interacts with FMRP, whose deactivation is responsible for Fragile X syndrome; an abnormality associated with learning problemes and autism in men. Four people were found by researchers who lacked a functioning copy of the TOP3B gene and they had been diagnosed either with learning problems or schizophrenia.
–1.4 megabase duplication on chromosome 7 (7q11.23) (Elsevier, 2014) – this gene increases the risk of exhibiting schizophrenia an astonishing 10x. In addition to schizophrenia, autism and cognitive developmental problems are associated with chromosome 7. This provides a great deal of support, the researchers say, to the notion that these disorders exhibit a neurodevelopmental commonality. Abnormal numbers of gene copies of 70 gene variants were implicated in early-onset developmental problems such as autism-spectrum disorders and intellectual deficit disorders.
-Chromosome 16p13.11 heterozygous deletion – 10% increase of developing schizophrenia.
–Chromosome 22 (velocardiofacial syndrome region) – A deletion of a small part of chromosome 22, leading to something known as 22q11.2 deletion syndrome, causes individuals to have velocardiofacial syndrome. 32% of those diagnosed with this genetic disorder develop schizophrenia. Particularly, those who exhibited progressive loss of temporal cortex gray matter were more likely to exhibit symptoms of psychosis.
The following information on 22q11.2 deletion syndrome is from Anne S. Bassett, MD, FRCPC, Eva W. Chow, MD, FRCPC, […], and Linda Brzustowicz, MD’s paper “Schizophrenia and Genetics: New Insights.” The researchers note that 22q deletion syndrome (22qDS) is an example of a “clinically detectable genetic subtype of schizophrenia that may serve as a model to study the etiopathogenesis of schizophrenia, including the neurodevelopmental process involved.”
Chromosome 22 was the first chromosome to be sequenced. The researchers say that approximately 25% of those who have this deletion develop schizophrenia. The only group of people with a higher risk of developing schizophrenia are identical twins of individuals who have schizophrenia. While 22q11.2 microdeletions are quite common (by the estimate of the authors, the second most common genetic syndrome, second only to Down syndrome), it is 80 times more common in populations of schizophrenia than in non-schizophrenic populations. Around 1 in 50 patients exhibit the deletion.
40 percent of adult schizophrenics exhibit 22q11.2 deletion. It is especially among among schizophrenics who are also diagnosable with mental retardation, constituting around 9%. The authors note that the symptoms of 22qDS are variable and oftentimes quite mild. They oftentimes exhibit themselves in abnormalities in the palate, neuromuscular problems, velopharyngeal insufficiency or (oftentimes mild) learning problems, although 35-40 percent of such people qualify as mildly retarded, with many others being severely mentally retarded.
90 percent of 22q11.2 deletions, the authors say, are de noto mutations without family histories of the syndrome. To say that it is “genetic,” therefore, does not necessarily (indeed, usually does not) mean that it is inherited. Clinical testing for the deletion became readily available in 1995. The discovery of 22q11.2 is revolutionary in that it is the first distinct, genetic subtype of schizophrenia. It can be distinguished from other forms of schizophrenia in that there is a lower family history of the disease, since it is usually a de novo mutation, and it includes lower IQ, equal distribution with respect to the sexes, and a lower rate of drug abuse.
The authors also point out the interesting phenomenon of distinct sets of genes correlated with schizophrenia which tend to be more common among specific geographical groups:
Now there is further evidence helping to confirm a chromosome 1q21-q22 schizophrenia susceptibility locus from multigenerational British and Icelandic families  and several new localizations of possible schizophrenia susceptibility genes (see Table 2). Besides 1q and 13q, there is significant evidence for linkage of schizophrenia to three more genomic regions from three different genetic isolate populations—the short (“p”) arm of chromosome 2 (2p13-14) in large Palauan families [32•], chromosome 2q37 in Finnish nuclear and larger families [33•], and chromosome 6q25 in a very large northern Swedish pedigree [34•]. A locus on chromosome 15q14 also reached a genome-wide level of significance in a reanalysis  of small European-American  and African-American families .
–Chromosome 2 (Centre for Addiction and Health, 2013) – Researchers believe that lesions on chromosome 2 may be responsible for a large percentage of schizophrenia diagnoses. Researchers believe they have identified numerous genetic abnormalities correlated with schizophrenia and autism-spectrum disorders.
Borderline personality disorder
–Chromosome 9 (University of Missouri-Columbia, 2008) – genetic material on chromosome 9 was correlated with behavioral characteristics of BPD. 711 pairs of siblings and 561 parents were examined through genetic linkage analysis of families. Of the chromosomal regions potentially linked with BPD, the evidence was strongest for a genetic linkage with chromosome 9. Another study involving 5,496 twins in Belgium, Australia and the Netherlands determined that 42 percent of BPD variation resulted from genetic factors and 58 percent from environmental factors.
The following information on the genetic predisposition of borderline personality disorder comes from a paper published by Eric Lis, Brian Greenfield, […], and Geoffrey Dougherty called “Neuroimaging and genetics of borderline personality disorder: a review.”
Most of the genes that have been relatively confidently linked with BPD are those which affect serotonin.
5-TT – 5-hydroxytryptamine (5-HT) transporter gene – Monkeys with the short allele of this gene are more likely to exhibit symptoms comparable to that of BPD when raised in non-nurturing environments, indicating an important gene-environment interaction.
5-HTTLPR – The short allele is associated with violent behavior in humans. Criminal offenders are more likely to have these short alleles. Those with eating disorders tend to exhibit higher rates of coexistent BPD and impulsive aggression when they have the shorter allele. One study found that every subject diagnosed with BPD possessed the short allele.
MAOA gene – This gene codes for the enzyme MAOA. It metabolizes numerous neurotransmitters, including, perhaps most importantly, serotonin. Those with genetic polymorphisms resulting in inadequate MAOI are more likely to exhibit criminality when raised in stressful environments.
–RORA (George Washington State University, 2013) – This gene is believed to regulate other genes associated with autism; that is, it is a “master regulator.” It is also known as a “nuclear hormone receptor.” Researchers are attempting to determine exactly which genes this gene regulates. It encodes a protein which is capable of regulating over 2,500 genes, many of which are known to play important roles in neuron development and function. 426 of its target genes are listed in AutismKB, which is a database of genes known to influence the development of autism. RORA transcriptionally regulates CYP19A1, A2BP1, HSD17B10, ITPR1, NLGN1 and NTRK2.
In a kind of domino effect, when RORA levels are reduced by half, these six genes are reduced in their expression. Postmortem brain tissue which exhibit decreased RORA levels from autistic individuals show a clear difference relative to non-autistic controls. The researchers believe that it is under negative regulation by androgen and positive regulation by estrogen, which may be why autism tends to affect males more.
–CHD8 (The Mount Sinai Hospital, 2012)
–SNC2A (The Mount Sinai Hospital, 2012)
–KATNAL2 (The Mount Sinai Hospital, 2012)
CHD8, SNC2A and KATNAL2 were discovered with the hope of exome sequencing. In this process, the “exome,” which refers to all the protein coding regions of the genome, are analyzed. The researchers say that 10 percent of the genes responsible for autism have been discovered. These researchers say that “de novo” mutations are responsible for a great deal of autism cases. These are cases that result from sperm or egg mutations. In this case, the researchers say that many mutations linked with autism-spectrum disorders are of paternal origin, supporting research which suggests a link between paternal age and the onset of autism in offspring.
–NCAN (Neurocan) (Cell Press, 2011) – This gene was significantly correlated with a diagnosis of bipolar disorder in thousands of patients. The mouse veresion of the gene is believed to be involved in neuronal adhesion and migration. This is expressed a great deal in areas of the brain that are associated with emotion regulation and cognition.
One researcher (Universität Bonn, 2012) found this gene correlated specifically with manic symptoms, as opposed to the depressive phases of bipolar disorder. Mice with the NCAN gene knocked out exhibited only manic, rather than depressive, symptoms. They exhibited higher levels of risk-taking behavior and were much more active. They also tended towards reward-seeking behavior much more. When the mice were given lithium, they were no longer hyperactive at all. The researchers therefore think that manic symptoms are the result of an abnormality in the NCAN protein in humans.
–PDE10A (Scripps Research Institute, 2012)
–DISC1 (Scripps Research Institute, 2012)
–GNAS (Scripps Research Institute, 2012)
Genes from 1,172 individuals diagnosed with bipolar disorder I were studied and 516 with bipolar disorder II, as well as 1,728 controls. Variants in the DISC1 and GNAS genes were associated with bipolar disorder II and variants in the PDE10A gene were associated with bipolar disorder I. PDE10A is located in the striatum, a region of the brain correlated with learning, memory, motivation and decision making.
The PBRM1 gene, locus of chromosome 3p21.1 (Elsevier, 2012) – This locus has previously been correlated with depression and schizophrenia. Unlike most studies which tend to correlate genetic risks for bipolar disorder with risks for schizophrenia, this study did not find such a correlation.
The study involved 28,000 subjects from 36 research centers. Evangelos Vassos (Elsevier, 2012) notes that the last few years have seen about two dozen genetic loci which are correlated with bipolar disorder and schizophrenia. Half of them (around 12) are correlated with both schizophrenia and bipolar disorder. The two disorders therefore seem to share many of the same genetic loci.
The author of the study notes that the gene is important for the study of epigentics because it “codes for a protein that is involved in chromatin remodeling or “epigenetics,” meaning that it influences the ability of a variety of environmental exposures to influence the expression of a range of genes”(Elsevier, 2012).
–The Slynar gene, on chromosome 12 (University College London, 2006) – 10 percent of those diagnosed with bipolar disorder have this gene. Mutations of the gene produce an abnormal effect in the brain. Researchers do not yet know what sorts of mutations produce this abnormality, however.
–FAT (University of New South Sales, 2006) – The FAT gene is responsible for coding a protein which hcelps to connect brain cells together. Researchers have found that it holds an important clue to bipolar didsorder, because the author of this study believes that lithium exerts its effects by affecting the expression of the FAT gene.
Several studies have implicated the gene regions:
ANK3 (Whiteman, 2014):
ODZ4 (Whiteman, 2014):
TRANK1 (Whiteman, 2014):
Recently, two other genetic regions were identified:
ADCY2 (Whiteman, 2014) – Exists on chromosome 5. It plays a role in signalling between nerve cells.
MIR2113-POU3F2 (Whiteman, 2014)– Exists on chromosome 6
–PCLO (Piccolo) (Elsevier, 2011) – This gene is a member of a family of proteins located at the tips of nerve cells. It helps nerve cells release chemical messengers. Some researchers believe studying this gene may yield insult into understanding the genesis of bipolar disorder. Researchers believe, specifically, that a variation in the gene contributes to its genesis after correlating a genetic marker close to the gene, SNP rs12338494, with bipolar disorder. They did this by comparing expression patterns of genes in postmortem cortical tissue in those who had been diagnosed with the disease with those who had not.
–Long variant of the 5-HTTLPR polymorphism – A study conducted by W.C. Nikkelen Sanne, Helen G.M. Vossen, Patti M. Valkenburg, Fleur P. Velders, Dafna A. Windhorst, Vincent V. Jaddoe, Albert Hofman, Frank C. Verhulst and Henning Tiemeier conducted a study on 1,612 Dutch children between the ages of 5-9 and concluded that those who possess the long variant of the 5-HTTLPR are more susceptible to high consumption of violent media and ADHD-related behaviors.
Researchers (BioMed Central, 2010) also correlated 5HTTLPR with self-blame in children relative to parental conflicts in a study of 304 youths. Those who had variants of this region correlated with both unusually high and unusually low serotonergic activity exhibited ADHD symptoms. 5HTTLPR “is a functional genetic region responsible for regulating the production of a protein that transports the neurotransmitter serotonin” and “has previously been linked to a range of neuropsychiatric disorders and personality traits.”
–The 48 base pair (bp) repeat polymorphism in the dopamine receptor D4 (DRD4) gene (BMC Evolutionary Biology) –
–DRD4 7R allele (BMC Evolutionary Biology) – the aforementioned researchers believe this to be associated with ADHD and drug and food craving, as well as novelty-seeking.
Researchers believe the two aforementioned genetic polymorphisms in dopamine receptor genes is positively correlated with better health in Kenyan nomads, whereas they believe it is correlated with malnourished in their sedentary counterparts. The DRD4 gene codes for a dopamine receptor, and is therefore believed to be an important gene for the study of addiction, reward anticipation and impulsivity.
The 48 bp repeat polymorphism in the D4DR gene polymorphism’s third exon was correlated with novelty seeking. It was particularly associated with the long alleles of the polymorphic exon III repeat sequence of D4DR. This latter study was carried out by Ono Y, Manki H, Yoshimura K, Muramatsu T, Mizushima H, Higuchi S, Yagi G, Kanba S, and Asai M.
Protein tyrosine phosphokinase (PTPRD) (Johns Hopkins Medicine, 2014) – 1,400 people diagnosed with OCD, as well as 1,000 close relatives, were studied on a genetic level. PTPRD was significantly correlated with a diagnosis of OCD. The gene is also associated with ADHD.
SLITRK (Johns Hopkins Medicine, 2014) – PTPRD works with SLITRK and is associated with OCD in animals.
The following information on the genetics of OCD comes from “Genetics of OCD” by Gerald Nestadt, Maco Grados and J.F. Samuels (2010).
–SLC6A4-Ile425Val – A serotonin transporter coding region variant correlated not only with OCD but with other mental abnormalities such as Asperger’s syndrome, autism and anorexia nervous. The study cited showed that those with this coding region variant as well as the “more highly transcribed allele of the serotonin promoter polymorphism” exhibited unusually severe and treatment resistant OCD. Two other studies supported this genetic correlation with OCD.
Sapap3 – A genetic deletion of this postsynaptic scaffolding protein at excitatory synapses is correalted with compulsive grooming in mice, and these behaviors are corrected with SSRI therapy. They cite another study that suggests that an SNP for this gene in humans is associated with compulsive grooming.
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Elsevier. (2014, February 20). Schizophrenia: Gathering clues to rare gene variants contributing to disease. ScienceDaily. Retrieved June 25, 2014 from www.sciencedaily.com/releases/2014/02/140220083151.htm
The Mount Sinai Hospital / Mount Sinai School of Medicine. (2012, April 4). Mutations in three genes linked to autism spectrum disorders. ScienceDaily. Retrieved June 25, 2014 from www.sciencedaily.com/releases/2012/04/120404133656.htm
University of Missouri-Columbia. (2008, December 20). Possible Genetic Causes Of Borderline Personality Disorder Identified. ScienceDaily. Retrieved June 25, 2014 from www.sciencedaily.com/releases/2008/12/081216114100.htm
Sanne W. C. Nikkelen1,*, Helen G. M. Vossen1, Patti M. Valkenburg1, Fleur P. Velders2, Dafna A. Windhorst2,3, Vincent W. V. Jaddoe2,4,5, Albert Hofman4, Frank C. Verhulst6 andHenning Tiemeier4,6
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University College London. (2006, October 3). New Gene Linked To Bipolar Disorder. ScienceDaily. Retrieved June 25, 2014 from www.sciencedaily.com/releases/2006/10/061003085831.htm
University of New South Wales. (2006, January 13). FAT Chance Of Becoming Manic-depressive. ScienceDaily. Retrieved June 25, 2014 from www.sciencedaily.com/releases/2006/01/060113111705.htm
Universität Bonn. (2012, September 1). Flying high: Researchers decipher manic gene. ScienceDaily. Retrieved June 25, 2014 from www.sciencedaily.com/releases/2012/09/120901084947.htm
Wellcome Trust Sanger Institute. (2013, August 4). Distinct brain disorders biologically linked: Disruption to the gene TOP3B increases susceptibility to schizophrenia and a learning disorder. ScienceDaily. Retrieved June 25, 2014 from www.sciencedaily.com/releases/2013/08/130804144420.htm
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Children’s Hospital of Philadelphia. (2010, May 10). Genes found for schizophrenia are involved in brain signaling. ScienceDaily. Retrieved June 26, 2014 from www.sciencedaily.com/releases/2010/05/100510151342.htm
RIKEN. (2014, January 2). Jumping DNA in brain may be cause of schizophrenia. ScienceDaily. Retrieved June 27, 2014 from www.sciencedaily.com/releases/2014/01/140102133148.htm
Anne S. Bassett, MD, FRCPC, Eva W. Chow, MD, FRCPC, […], and Linda Brzustowicz, MD. Schizophrenia and genetics: New Insights. Curre Psychiatry Rep. Aug 2002; 4(4): 307-314.
Eric Lis, Brian Greenfield, […], and Geoffrey Dougherty. Neuroimaging and genetics of borderline personality disorder: a review. J Psychiatry Neurosci. May 2007; 32(3): 162-173.
Columbia University Medical Center. (2014, May 28). Uncovering Clues to the Genetic Cause of Schizophrenia. ScienceDaily. Retrieved June 27, 2014 from www.sciencedaily.com/releases/2014/05/140528132701.htm
Elsevier. (2012, October 10). Does immune dysfunction contribute to schizophrenia? Genetic findings from new study. ScienceDaily. Retrieved June 25, 2014 from www.sciencedaily.com/releases/2012/10/121010102033.htm
Whiteman, Honor (2014). Researchers discover two new genetic regions for bipolar disorder. Retrieved from: http://www.medicalnewstoday.com/articles/273877.php
Elsevier. (2011, February 24). New clue to the genetics of bipolar disorder: Piccolo. ScienceDaily. Retrieved June 28, 2014 from www.sciencedaily.com/releases/2011/02/110223122419.htm
Gerald Nestadt, Maco Grados, and J.F. Samuels. Genetics of OCD. Psychiatr Clin North Am. Mar 2010; 33(1): 141-158.