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

Matthew James Hill, Elaine M Kenny, Siobhan Roche, Derek W Morris, Aiden Corvin, Ziarih Hawi, Michael Gill, Richard J Anney

Research output: Contribution to journalArticleResearchpeer-review

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Abstract

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.
Original languageEnglish
Pages (from-to)281 - 286
Number of pages6
JournalPsychiatric Genetics
Volume21
Issue number6
DOIs
Publication statusPublished - 2011
Externally publishedYes

Cite this

Hill, Matthew James ; Kenny, Elaine M ; Roche, Siobhan ; Morris, Derek W ; Corvin, Aiden ; Hawi, Ziarih ; Gill, Michael ; Anney, Richard J. / Allelic expression imbalance of the schizophrenia susceptibility gene CHI3L1: evidence of cis-acting variation and tissue specific regulation. In: Psychiatric Genetics. 2011 ; Vol. 21, No. 6. pp. 281 - 286.
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abstract = "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.",
author = "Hill, {Matthew James} and Kenny, {Elaine M} and Siobhan Roche and Morris, {Derek W} and Aiden Corvin and Ziarih Hawi and Michael Gill and Anney, {Richard J}",
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Allelic expression imbalance of the schizophrenia susceptibility gene CHI3L1: evidence of cis-acting variation and tissue specific regulation. / Hill, Matthew James; Kenny, Elaine M; Roche, Siobhan; Morris, Derek W; Corvin, Aiden; Hawi, Ziarih; Gill, Michael; Anney, Richard J.

In: Psychiatric Genetics, Vol. 21, No. 6, 2011, p. 281 - 286.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Allelic expression imbalance of the schizophrenia susceptibility gene CHI3L1: evidence of cis-acting variation and tissue specific regulation

AU - Hill, Matthew James

AU - Kenny, Elaine M

AU - Roche, Siobhan

AU - Morris, Derek W

AU - Corvin, Aiden

AU - Hawi, Ziarih

AU - Gill, Michael

AU - Anney, Richard J

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N2 - 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.

AB - 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.

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