Re-screening serotonin receptors for genetic variants identifies population and molecular genetic complexity.
We have re-screened the genes for the 5-HT1A, 5-HT2A, 5-HT2C, and 5-HT7 serotonin receptors for genetic variants in a large African-American and Caucasian-American population sample. We have identified eight novel variants in these genes including four that are predicted to cause amino acid substitutions. These variants are additional candidates for association studies of behavioral disorders such as depression and schizophrenia as well as quantitative personality traits. We have also detected some, but not all, previously identified variants in these genes suggesting that many previously identified variants are unique to specific populations. The results of this study, and previous screens of serotonin receptors, demonstrate that the genes for serotonin receptors display marked population and molecular genetic complexity. These levels of complexity may have a substantial effect on genetic association studies of human behavioral variability related to these genes. We discuss the implications of these findings and propose methods to address complexity in genetic association studies.
Glatt
Charles E
CE
UCLA Center for Neurobehavioral Genetics, Gonda Center, Los Angeles, California, USA. cglatt@mednet.ucla.edu
Tampilic
Maricel
M
Christie
Carroll
C
DeYoung
Joe
J
Freimer
Nelson B
NB
D001741:Black or African American / Q000235:genetics; D000483:Alleles; D000595:Amino Acid Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D005820:Genetic Testing; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D001523:Mental Disorders / Q000175:diagnosis / Q000235:genetics; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics; D011985:Receptors, Serotonin / Q000235:genetics*; D017385:Sequence Homology; D044465:White People / Q000235:genetics
D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A; D004247:DNA