Allelic expression imbalance of the schizophrenia susceptibility gene CHI3L1: evidence of cis-acting variation and tissue specific regulation

作者：Hill Matthew James^*; Kenny Elaine; Roche Siobhan; Morris Derek W; Corvin Aiden; Hawi Ziarih; Gill Michael; Anney Richard J L

来源：Psychiatric Genetics, 2011, 21(6): 281-286.

DOI：10.1097/YPG.0b013e328348045b

• allelic expression
• molecular genetics
• regulatory polymorphism
• schizophrenia

Objective To identify cis-acting regulatory variants influencing the expression of the schizophrenia susceptibility gene chitinase 3-like 1 gene (CHI3L1) in human lymphoblasts and post-mortem brain tissue.
Methods To investigate the role of cis-acting regulatory variants in controlling gene expression of CHI3L1 we quantified relative allelic abundance in individuals heterozygous for the transcribed polymorphism rs880633. Allelic quantification was performed using RNA derived from 45 individuals from the HapMap CEU panel and 41 postmortem brain samples. Association of allelic imbalance with genetic variants was determined at a gene-wide level for the HapMap samples using available genotyping data.
Results Expression of the CHI3L1 transcript is under the control of potently acting cis-variation in lymphoblasts. Polymorphisms in the promoter region of CHI3L1 were significantly associated with this allelic imbalance. In the single postmortem brain tissue investigated, only moderate allelic imbalance was detected and was restricted to a small number of individuals.
Conclusion CHI3L1 contains common cis-acting regulatory variants that affect gene expression in lymphoblasts. A previously identified schizophrenia susceptibility variant was significantly associated with allelic imbalance in lymphoblasts. These findings do not support the notion that the schizophrenia-associated CHI3L1 variants influence gene expression in BA46 of the adult brain. We confirm that CHI3L1 contains cis-acting variation but is subject to tissue-specific regulation.

• 出版日期2011-12