Genetics of Schizophrenia: What Do We Know: Researchers Are Discovering Clues to Predict Susceptibility, Improve Treatment

Genetic factors play a major role in the etiology and development of schizophrenia. Genetic linkage studies and twin studies have estimated the heritability of schizophrenia to be 70% to 90%. (1) Research on the genetic underpinnings of schizophrenia has accelerated since the Human Genome Project was completed in 2001, which opened the door to expanding our understanding of molecular mechanisms of human diseases. Experts have hailed the dawn of personalized medicine, (2) hoping that we will be able to use knowledge of the human genome to tailor individual treatment. In this article we review some significant recent findings in genetics of schizophrenia. Gene names are italicized and proteins coded by genes are not. The names, functions, and locations of all genes included in this article appear in the Table (page 26). For a glossary of genetic terms, -see this article at CurrentPsychiatry.com. Focusing on single nucleotide polymorphisms Genetic research of diseases previously relied on linkage studies, which focus on linking a chromosome region to transmission of a particular trait across multiple familial generations. This approach has identified several genomic regions that may be associated with schizophrenia, but most of these regions contain multiple genes and are not specific to schizophrenia. Today, many genetic studies examine variations of a single nucleotide in the DNA sequence, ie, a change of 1 letter in a particular location on the DNA chain. Single nucleotide polymorphisms (SNPs)--relatively common DNA variations found in >5% of the population--have been a major focus of psychiatric genetics in the past decade. Technology now allows researchers to simultaneously genotype millions of SNPs across the genome, producing tremendous power to investigate the entire genome in relation to a phenotype (a disease or a trait) in genome-wide association studies (GWAS). (3) GWAS do not require an a priori hypothesis regarding which regions or genes may be important, and have yielded many novel genetic variants implicated in schizophrenia. Susceptibility genes Genetic researchers initially hoped to find that one or a few genes are responsible for schizophrenia. However, recent research revealed that many genes may be involved in susceptibility to schizophrenia, and that a particular gene may contribute to the risk of not only schizophrenia but also other psychiatric disorders such as bipolar disorder (BD). Table Select genes and their functions Gene Name Location Location Function(s) CACNA1C Calcium channel, 12p13.3 Calcium channels voltage-dependent, L type, mediate the influx of alpha 1C sub-unit calcium ions into the cell upon membrane polarization COMT Catechol-O-methyttransferase 22q Key enzyme in 11.21 degradation of dopamine and norepinephrine CSMD1 CUB and Sushi multiple 8p23.2 One of the proteins domains 1 that modulate the classical complement pathway, part of the immune system CYP2D6 Cytochrome P450 2D6 22q13.1 Key enzyme in drug metabolism C10orf26 Chromosome 10 open reading 10q24.32 Unknown frame 26 DISC1 Disrupted In schizophrenia 1 1q42 Neurite outgrowth, cortical development synaptic function DRD1 Dopamine receptor D1 5q35. …