PMID- 32066700 OWN - NLM STAT- MEDLINE DCOM- 20210618 LR - 20220420 IS - 2158-3188 (Electronic) IS - 2158-3188 (Linking) VI - 10 IP - 1 DP - 2020 Feb 5 TI - Genome-wide study of immune biomarkers in cerebrospinal fluid and serum from patients with bipolar disorder and controls. PG - 58 LID - 10.1038/s41398-020-0737-6 [doi] LID - 58 AB - Bipolar disorder is a common, chronic psychiatric disorder. Despite high heritability, there is a paucity of identified genetic risk factors. Immune biomarkers are under more direct genetic influence than bipolar disorder. To explore the genetic associations with immune biomarker levels in cerebrospinal fluid (CSF) and blood serum which previously showed differences in bipolar disorder, we performed a study involving 291 individuals (184 bipolar disorder patients and 107 controls). The biomarkers assayed in both CSF and serum were: chitinase-3-like protein-1 (YKL-40), monocyte chemoattractant protein-1 (MCP-1), soluble cluster of differentiation (sCD14), tissue inhibitor of metalloproteinases-1 and 2 (TIMP-1 and TIMP-2). C-reactive protein (CRP) was only quantified in serum, and interleukin 8 (IL-8) measures were only available in CSF. Genome-wide association studies were conducted using PLINK for each of three genotyping waves and incorporated covariates for population substructure, age, sex, and body mass index (BMI). Results were combined by meta-analysis. Genome-wide significant associations were detected for all biomarkers except TIMP-1 and TIMP-2 in CSF. The strongest association in CSF was found for markers within the CNTNAP5 gene with YKL-40 (rs150248456, P = 2.84 x 10(-10)). The strongest association in serum was also for YKL-40 but localized to the FANCI gene (rs188263039, P = 5.80 x 10(-26)). This study revealed numerous biologically plausible genetic associations with immune biomarkers in CSF and blood serum. Importantly, the genetic variants regulating immune biomarker levels in CSF and blood serum differ. These results extend our knowledge of how biomarkers showing alterations in bipolar disorder are genetically regulated. FAU - Zhang, Ruyue AU - Zhang R AUID- ORCID: 0000-0001-5747-9428 AD - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. FAU - Song, Jie AU - Song J AD - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. FAU - Isgren, Anniella AU - Isgren A AD - Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Molndal, Sweden. FAU - Jakobsson, Joel AU - Jakobsson J AD - Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Molndal, Sweden. FAU - Blennow, Kaj AU - Blennow K AD - Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Molndal, Sweden. AD - Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Molndal, Sweden. FAU - Sellgren, Carl M AU - Sellgren CM AD - Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. AD - Centre for Psychiatry Research, Karolinska Institutet, & Stockholm Health Care Services, Stockholm County Council, Karolinska University Hospital, Stockholm, Sweden. FAU - Zetterberg, Henrik AU - Zetterberg H AD - Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Molndal, Sweden. AD - Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Molndal, Sweden. AD - Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London, UK. AD - UK Dementia Research Institute at UCL, London, UK. FAU - Bergen, Sarah E AU - Bergen SE AUID- ORCID: 0000-0002-5888-0034 AD - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. sbergen@gmail.com. FAU - Landen, Mikael AU - Landen M AUID- ORCID: 0000-0002-4496-6451 AD - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. AD - Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Molndal, Sweden. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't DEP - 20200205 PL - United States TA - Transl Psychiatry JT - Translational psychiatry JID - 101562664 RN - 0 (Biomarkers) SB - IM MH - Biomarkers MH - *Bipolar Disorder/genetics MH - *Genome-Wide Association Study MH - Humans MH - Serum PMC - PMC7026056 COIS- H.Z. has served at scientific advisory boards for Roche Diagnostics, Wave, Samumed and CogRx, has given lectures in symposia sponsored by Biogen and Alzecure, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg (all unrelated to the submitted work). J.J. has been an employee of AstraZeneca, Apr 2017-Jan 2019 (not related to the submitted work). K.B. has served as a consultant or at advisory boards for Alector, Alzheon, CogRx, Biogen, Lilly, Novartis and Roche Diagnostics, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg, all unrelated to the work presented in this paper. C.S.M. is a co-founder of Outermost Therapeutics (unrelated to the submitted work). The other authors declare no conflict of interest. EDAT- 2020/02/19 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/02/05 CRDT- 2020/02/19 06:00 PHST- 2019/08/11 00:00 [received] PHST- 2020/01/20 00:00 [accepted] PHST- 2020/01/13 00:00 [revised] PHST- 2020/02/19 06:00 [entrez] PHST- 2020/02/19 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/02/05 00:00 [pmc-release] AID - 10.1038/s41398-020-0737-6 [pii] AID - 737 [pii] AID - 10.1038/s41398-020-0737-6 [doi] PST - epublish SO - Transl Psychiatry. 2020 Feb 5;10(1):58. doi: 10.1038/s41398-020-0737-6.