Journal article
Targeted sequencing of the LRRTM gene family in suicide attempters with bipolar disorder
American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.183(2), pp.128-139
03/2020
DOI: 10.1002/ajmg.b.32767
PMCID: PMC8380126
PMID: 31854516
Abstract
Glutamatergic signaling is the primary excitatory neurotransmission pathway in the brain, and its relationship to neuropsychiatric disorders is of considerable interest. Our previous attempted suicide genome‐wide association study, and numerous studies investigating gene expression, genetic variation, and DNA methylation have implicated aberrant glutamatergic signaling in suicide risk. The glutamatergic pathway gene LRRTM4 was an associated gene identified in our attempted suicide genome‐wide association study, with association support seen primarily in females. Recent evidence has also shown that glutamatergic signaling is partly regulated by sex‐related hormones. The LRRTM gene family encodes neuronal leucine‐rich transmembrane proteins that localize to and promote glutamatergic synapse development. In this study, we sequenced the coding and regulatory regions of all four LRRTM gene members plus a large intronic region of LRRTM4 in 476 bipolar disorder suicide attempters and 473 bipolar disorder nonattempters. We identified two male‐specific variants, one female‐ and five male‐specific haplotypes significantly associated with attempted suicide in LRRTM4. Furthermore, variants within significant haplotypes may be brain expression quantitative trait loci for LRRTM4 and some of these variants overlap with predicted hormone response elements. Overall, these results provide supporting evidence for a sex‐specific association of genetic variation in LRRTM4 with attempted suicide.
Details
- Title: Subtitle
- Targeted sequencing of the LRRTM gene family in suicide attempters with bipolar disorder
- Creators
- Rachel D Reichman - University of Iowa Carver College of MedicineSophia C Gaynor - University of Iowa Carver College of MedicineEric T Monson - University of Iowa Carver College of MedicineMarie E Gaine - Iowa Neuroscience Institute, Carver College of Medicine, University of IowaMeredith G Parsons - University of Iowa Carver College of MedicinePeter P Zandi - Johns Hopkins Bloomberg School of Public HealthJames B Potash - Johns Hopkins School of MedicineVirginia L Willour - University of Iowa Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.183(2), pp.128-139
- DOI
- 10.1002/ajmg.b.32767
- PMID
- 31854516
- PMCID
- PMC8380126
- NLM abbreviation
- Am J Med Genet B Neuropsychiatr Genet
- ISSN
- 1552-4841
- eISSN
- 1552-485X
- Publisher
- John Wiley & Sons, Inc; Hoboken, USA
- Number of pages
- 12
- Grant note
- National Institute of Mental Health (R21 MH092791) American Foundation for Suicide Prevention (AFSP) (PDF‐0‐067‐12) University of Iowa Medical Scientist Training Program (MSTP) (GM007337) University of Iowa Interdisciplinary Graduate Program in Genetics
- Language
- English
- Date published
- 03/2020
- Academic Unit
- Psychiatry; Pathology; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984065466702771
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