| Title: |
Identification of Novel, Replicable Genetic Risk Loci for Suicidal Thoughts and Behaviors Among US Military Veterans |
| Authors: |
Kimbrel, Nathan A.; Ashley-Koch, Allison E.; Qin, Xue J.; Lindquist, Jennifer H.; Garrett, Melanie E.; Dennis, Michelle F.; Hair, Lauren P.; Huffman, Jennifer E.; Jacobson, Daniel A.; Madduri, Ravi K.; Trafton, Jodie A.; Coon, Hilary; Docherty, Anna R.; Mullins, Niamh; Ruderfer, Douglas M.; Harvey, Philip D.; McMahon, Benjamin H.; Oslin, David W.; Beckham, Jean C.; Hauser, Elizabeth R.; Hauser, Michael A.; Agarwal, Khushbu; Aslan, Mihaela; Begoli, Edmond; Bhattacharya, Tanmoy; Brown, Ben; Calhoun, Patrick S.; Cheung, Kei-Hoi; Choudhury, Sutanay; Cliff, Ashley M.; Cohn, Judith D.; Crivelli, Silvia; Cuellar-Hengartner, Leticia; Deangelis, Haedi E.; Dhaubhadel, Sayera; Finley, Patrick D.; Ganguly, Kumkum; Garvin, Michael R.; Gelernter, Joel E.; Harvey, Phillip D.; Hengartner, Nick W.; Jones, Piet C.; Kainer, David |
| Source: |
JAMA Psychiatry ; volume 80, issue 2, page 135 ; ISSN 2168-622X |
| Publisher Information: |
American Medical Association (AMA) |
| Publication Year: |
2023 |
| Description: |
Importance Suicide is a leading cause of death; however, the molecular genetic basis of suicidal thoughts and behaviors (SITB) remains unknown. Objective To identify novel, replicable genomic risk loci for SITB. Design, Setting, and Participants This genome-wide association study included 633 778 US military veterans with and without SITB, as identified through electronic health records. GWAS was performed separately by ancestry, controlling for sex, age, and genetic substructure. Cross-ancestry risk loci were identified through meta-analysis. Study enrollment began in 2011 and is ongoing. Data were analyzed from November 2021 to August 2022. Main Outcome and Measures SITB. Results A total of 633 778 US military veterans were included in the analysis (57 152 [9%] female; 121 118 [19.1%] African ancestry, 8285 [1.3%] Asian ancestry, 452 767 [71.4%] European ancestry, and 51 608 [8.1%] Hispanic ancestry), including 121 211 individuals with SITB (19.1%). Meta-analysis identified more than 200 GWS ( P < 5 × 10 −8 ) cross-ancestry risk single-nucleotide variants for SITB concentrated in 7 regions on chromosomes 2, 6, 9, 11, 14, 16, and 18. Top single-nucleotide variants were largely intronic in nature; 5 were independently replicated in ISGC, including rs6557168 in ESR1, rs12808482 in DRD2, rs77641763 in EXD3 , rs10671545 in DCC , and rs36006172 in TRAF3. Associations for FBXL19 and AC018880 .2 were not replicated. Gene-based analyses implicated 24 additional GWS cross-ancestry risk genes, including FURIN, TSNARE1, and the NCAM1-TTC12-ANKK1-DRD2 gene cluster. Cross-ancestry enrichment analyses revealed significant enrichment for expression in brain and pituitary tissue, synapse and ubiquitination processes, amphetamine addiction, parathyroid hormone synthesis, axon guidance, and dopaminergic pathways. Seven other unique European ancestry–specific GWS loci were identified, 2 of which ( POM121L2 and METTL15 / LINC02758 ) were replicated. Two additional GWS ancestry-specific loci were identified within the ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1001/jamapsychiatry.2022.3896 |
| Availability: |
https://doi.org/10.1001/jamapsychiatry.2022.3896; https://jamanetwork.com/journals/jamapsychiatry/articlepdf/2799487/jamapsychiatry_kimbrel_2022_oi_220079_1675180157.68937.pdf |
| Accession Number: |
edsbas.767837F6 |
| Database: |
BASE |