Genetic variations in the serotonergic system contribute to amygdala volume in humans.
The amygdala plays a critical role in emotion processing and psychiatric disorders associated with emotion dysfunction. Accumulating evidence suggests that amygdala structure is modulated by serotonin-related genes. However, there is a gap between the small contributions of single loci (less than 1%) and the reported 63-65% heritability of amygdala structure. To understand the "missing heritability," we systematically explored the contribution of serotonin genes on amygdala structure at the gene set level. The present study of 417 healthy Chinese volunteers examined 129 representative polymorphisms in genes from multiple biological mechanisms in the regulation of serotonin neurotransmission. A system-level approach using multiple regression analyses identified that nine SNPs collectively accounted for approximately 8% of the variance in amygdala volume. Permutation analyses showed that the probability of obtaining these findings by chance was low (p = 0.043, permuted for 1000 times). Findings showed that serotonin genes contribute moderately to individual differences in amygdala volume in a healthy Chinese sample. These results indicate that the system-level approach can help us to understand the genetic basis of a complex trait such as amygdala structure.
State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University Beijing, China ; Brainnetome Center, Institute of Automation, Chinese Academy of Sciences Beijing, China ; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences Beijing, China.
Jin
J
Li
State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University Beijing, China ; Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University Beijing, China.
Chunhui
C
Chen
Department of Psychology and Social Behavior, University of California, Irvine Irvine, CA, USA.
Karen
K
Wu
Key Laboratory of Behavioral Science, Institute of Psychology, Chinese Academy of Sciences Beijing, China.
Mingxia
M
Zhang
State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University Beijing, China ; Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University Beijing, China.
Bi
B
Zhu
Department of Psychology and Social Behavior, University of California, Irvine Irvine, CA, USA.
Chuansheng
C
Chen
Department of Biological Chemistry, University of California, Irvine Irvine, CA, USA ; Institute of Genomics and Bioinformatics, University of California, Irvine Irvine, CA, USA.
Robert K
RK
Moyzis
State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University Beijing, China ; Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University Beijing, China.
Qi
Q
Dong
amygdala; brain structure; gene; missing heritability; serotonin