Systems genetics analysis of pharmacogenomics variation during antidepressant treatment

TY - JOUR

T1 - Systems genetics analysis of pharmacogenomics variation during antidepressant treatment

AU - Madsen, M. B.

AU - Kogelman, L. J. A.

AU - Kadarmideen, H. N.

AU - Rasmussen, H. B.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants, but the efficacy of the treatment varies significantly among individuals. It is believed that complex genetic mechanisms play a part in this variation. We have used a network based approach to unravel the involved genetic components. Moreover, we investigated the potential difference in the genetic interaction networks underlying SSRI treatment response over time. We found four hub genes (ASCC3, PPARGC1B, SCHIP1 and TMTC2) with different connectivity in the initial SSRI treatment period (baseline to week 4) compared with the subsequent period (4-8 weeks after initiation), suggesting that different genetic networks are important at different times during SSRI treatment. The strongest interactions in the initial SSRI treatment period involved genes encoding transcriptional factors, and in the subsequent period genes involved in calcium homeostasis. In conclusion, we suggest a difference in genetic interaction networks between initial and subsequent SSRI response.

AB - Selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants, but the efficacy of the treatment varies significantly among individuals. It is believed that complex genetic mechanisms play a part in this variation. We have used a network based approach to unravel the involved genetic components. Moreover, we investigated the potential difference in the genetic interaction networks underlying SSRI treatment response over time. We found four hub genes (ASCC3, PPARGC1B, SCHIP1 and TMTC2) with different connectivity in the initial SSRI treatment period (baseline to week 4) compared with the subsequent period (4-8 weeks after initiation), suggesting that different genetic networks are important at different times during SSRI treatment. The strongest interactions in the initial SSRI treatment period involved genes encoding transcriptional factors, and in the subsequent period genes involved in calcium homeostasis. In conclusion, we suggest a difference in genetic interaction networks between initial and subsequent SSRI response.

U2 - 10.1038/tpj.2016.68

DO - 10.1038/tpj.2016.68

M3 - Journal article

C2 - 27752142

SN - 1470-269X

VL - 18

SP - 144

EP - 152

JO - The Pharmacogenomics Journal

JF - The Pharmacogenomics Journal

ER -