Stress-sensitive neurosignalling in depression: an integrated network biology approach to candidate gene selection for genetic association analysis
Genetic risk for depressive disorders is poorly understood despite consistent suggestions of a high heritable component. Most genetic studies have focused on risk associated with single variants, a strategy which has so far only yielded small (often non-replicable) risks for depressive disorders. In...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2012-07-01
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| Series: | Mental Illness |
| Subjects: | |
| Online Access: | http://www.pagepress.org/journals/index.php/mi/article/view/3636 |
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| author | J. Anke M. van Eekelen Justine A. Ellis Craig A. Olsson Craig E. Pennell Jeff Craig Richard Saffery Eugen Mattes |
| author_facet | J. Anke M. van Eekelen Justine A. Ellis Craig A. Olsson Craig E. Pennell Jeff Craig Richard Saffery Eugen Mattes |
| author_sort | J. Anke M. van Eekelen |
| collection | DOAJ |
| description | Genetic risk for depressive disorders is poorly understood despite consistent suggestions of a high heritable component. Most genetic studies have focused on risk associated with single variants, a strategy which has so far only yielded small (often non-replicable) risks for depressive disorders. In this paper we argue that more substantial risks are likely to emerge from genetic variants acting in synergy within and across larger neurobiological systems (polygenic risk factors). We show how knowledge of major integrated neurobiological systems provides a robust basis for defining and testing theoretically defensible polygenic risk factors. We do this by describing the architecture of the overall stress response. Maladaptation via impaired stress responsiveness is central to the aetiology of depression and anxiety and provides a framework for a systems biology approach to candidate gene selection. We propose principles for identifying genes and gene networks within the neurosystems involved in the stress response and for defining polygenic risk factors based on the neurobiology of stress-related behaviour. We conclude that knowledge of the neurobiology of the stress response system is likely to play a central role in future efforts to improve genetic prediction of depression and related disorders. |
| format | Article |
| id | doaj-art-da0c086a2f2f4125b45742882c54a862 |
| institution | Kabale University |
| issn | 2036-7457 2036-7465 |
| language | English |
| publishDate | 2012-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mental Illness |
| spelling | doaj-art-da0c086a2f2f4125b45742882c54a8622025-02-03T06:05:57ZengWileyMental Illness2036-74572036-74652012-07-0142e21e2110.4081/mi.2012.e21Stress-sensitive neurosignalling in depression: an integrated network biology approach to candidate gene selection for genetic association analysisJ. Anke M. van EekelenJustine A. EllisCraig A. OlssonCraig E. PennellJeff CraigRichard SafferyEugen MattesGenetic risk for depressive disorders is poorly understood despite consistent suggestions of a high heritable component. Most genetic studies have focused on risk associated with single variants, a strategy which has so far only yielded small (often non-replicable) risks for depressive disorders. In this paper we argue that more substantial risks are likely to emerge from genetic variants acting in synergy within and across larger neurobiological systems (polygenic risk factors). We show how knowledge of major integrated neurobiological systems provides a robust basis for defining and testing theoretically defensible polygenic risk factors. We do this by describing the architecture of the overall stress response. Maladaptation via impaired stress responsiveness is central to the aetiology of depression and anxiety and provides a framework for a systems biology approach to candidate gene selection. We propose principles for identifying genes and gene networks within the neurosystems involved in the stress response and for defining polygenic risk factors based on the neurobiology of stress-related behaviour. We conclude that knowledge of the neurobiology of the stress response system is likely to play a central role in future efforts to improve genetic prediction of depression and related disorders.http://www.pagepress.org/journals/index.php/mi/article/view/3636systems biology, emotion, behaviour, hypothalamic-pituitary-adrenal axis, the Raine Study |
| spellingShingle | J. Anke M. van Eekelen Justine A. Ellis Craig A. Olsson Craig E. Pennell Jeff Craig Richard Saffery Eugen Mattes Stress-sensitive neurosignalling in depression: an integrated network biology approach to candidate gene selection for genetic association analysis Mental Illness systems biology, emotion, behaviour, hypothalamic-pituitary-adrenal axis, the Raine Study |
| title | Stress-sensitive neurosignalling in depression: an integrated network biology approach to candidate gene selection for genetic association analysis |
| title_full | Stress-sensitive neurosignalling in depression: an integrated network biology approach to candidate gene selection for genetic association analysis |
| title_fullStr | Stress-sensitive neurosignalling in depression: an integrated network biology approach to candidate gene selection for genetic association analysis |
| title_full_unstemmed | Stress-sensitive neurosignalling in depression: an integrated network biology approach to candidate gene selection for genetic association analysis |
| title_short | Stress-sensitive neurosignalling in depression: an integrated network biology approach to candidate gene selection for genetic association analysis |
| title_sort | stress sensitive neurosignalling in depression an integrated network biology approach to candidate gene selection for genetic association analysis |
| topic | systems biology, emotion, behaviour, hypothalamic-pituitary-adrenal axis, the Raine Study |
| url | http://www.pagepress.org/journals/index.php/mi/article/view/3636 |
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