Identification of novel genome-wide associations for suicidality in UK Biobank, genetic correlation with psychiatric disorders and polygenic association with completed suicide

EBioMedicine

Volumn 41, Issue , 2019, Pages 517-525

  Strawbridge, Rona J ^a,b   Ward, Joey ^a   Ferguson, Amy ^a   Graham, Nicholas ^a   Shaw, Richard J ^a   Cullen, Breda ^a   Pearsall, Robert ^a   Lyall, Laura M ^a   Johnston, Keira J A ^a,c   Niedzwiedz, Claire L ^a   Pell, Jill P ^a   Mackay, Daniel ^a   Martin, Julie Langan ^a   Lyall, Donald M ^a   Bailey, Mark E S ^a   Smith, Daniel J ^a  

^a UNIVERSITY OF GLASGOW   (United Kingdom)

^b KAROLINSKA INSTITUTE   (Sweden)

^c UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ADULT; ARTICLE; CHILDHOOD TRAUMA; CHROMOSOME 11; CHROMOSOME 13; CHROMOSOME 9; COGNITION; COHORT ANALYSIS; CONTROLLED STUDY; DEPRESSION; DISEASE ASSESSMENT; FEMALE; GENE EXPRESSION; GENETIC ASSOCIATION; GENETIC CORRELATION; GENETIC LOAD; GENETIC RISK; GENETIC VARIABILITY; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HUMAN; MAJOR CLINICAL STUDY; MALE; MENTAL DISEASE; MENTAL HEALTH; MOOD DISORDER; NEUROSIS; PHENOTYPE; POLYGENIC RISK SCORE; PREVALENCE; PRIORITY JOURNAL; PSYCHIATRIC DIAGNOSIS; QUALITY CONTROL; SINGLE NUCLEOTIDE POLYMORPHISM; SOCIAL ISOLATION; SUICIDE; SUICIDE ATTEMPT; AGED; BIOBANK; GENETICS; MIDDLE AGED; PATHOLOGY; PSYCHOLOGY; SUICIDAL IDEATION; UNITED KINGDOM;

ADULT; AGED; BIOLOGICAL SPECIMEN BANKS; COHORT STUDIES; FEMALE; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HUMANS; MALE; MENTAL DISORDERS; MIDDLE AGED; POLYMORPHISM, SINGLE NUCLEOTIDE; SUICIDAL IDEATION; SUICIDE; SUICIDE, ATTEMPTED; UNITED KINGDOM;

EID: 85061112218     PISSN: None     EISSN: 23523964     Source Type: Journal    
DOI: 10.1016/j.ebiom.2019.02.005     Document Type: Article

References (44)

1. WHO, Summary tables of mortality estimates by cause, age and sex, globally and by region, 2000–2015. 2017.
2. Zalsman, G., Hawton, K., Wasserman, D., van Heeringen, K., Arensman, E., Sarchiapone, M., et al. Suicide prevention strategies revisited: 10-year systematic review. Lancet Psychiatry 3:7 (2016), 646–659.
3. Turecki, G., The molecular bases of the suicidal brain. Nat Rev Neurosci 15:12 (2014), 802–816.
4. Nock, M.K., Borges, G., Bromet, E.J., Alonso, J., Angermeyer, M., Beautrais, A., et al. Cross-national prevalence and risk factors for suicidal ideation, plans and attempts. Br J Psychiatry 192:2 (2008), 98–105.
5. Yoshimasu, K., Kiyohara, C., Miyashita, K., Stress Research Group of the Japanese Society for H, Suicidal risk factors and completed suicide: meta-analyses based on psychological autopsy studies. Environ Health Prev Med 13:5 (2008), 243–256.
6. Mann, J.J., Apter, A., Bertolote, J., Beautrais, A., Currier, D., Haas, A., et al. Suicide prevention strategies: a systematic review. JAMA 294:16 (2005), 2064–2074.
7. Hawton, K., Saunders, K.E., O'Connor, R.C., Self-harm and suicide in adolescents. Lancet 379:9834 (2012), 2373–2382.
8. Berg, L., Rostila, M., Hjern, A., Parental death during childhood and depression in young adults - a national cohort study. J Child Psychol Psychiatry 57:9 (2016), 1092–1098.
9. Arsenault-Lapierre, G., Kim, C., Turecki, G., Psychiatric diagnoses in 3275 suicides: a meta-analysis. BMC Psychiatry, 4, 2004, 37.
10. Kendler, K.S., Genetic and environmental pathways to suicidal behavior: reflections of a genetic epidemiologist. Eur Psychiatry 25:5 (2010), 300–303.
11. Franklin, J.C., Ribeiro, J.D., Fox, K.R., Bentley, K.H., Kleiman, E.M., Huang, X., et al. Risk factors for suicidal thoughts and behaviors: a meta-analysis of 50 years of research. Psychol Bull 143:2 (2017), 187–232.
12. Brent, D.A., Melhem, N., Familial transmission of suicidal behavior. Psychiatr Clin North Am 31:2 (2008), 157–177.
13. Brent, D.A., Bridge, J., Johnson, B.A., Connolly, J., Suicidal behavior runs in families. A controlled family study of adolescent suicide victims. Arch Gen Psychiatry 53:12 (1996), 1145–1152.
14. Galfalvy, H., Haghighi, F., Hodgkinson, C., Goldman, D., Oquendo, M.A., Burke, A., et al. A genome-wide association study of suicidal behavior. Am J Med Genet B Neuropsychiatr Genet 168:7 (2015), 557–563.
15. Kimbrel, N.A., Garrett, M.E., Dennis, M.F., Va Mid-Atlantic Mental Illness Research E, Clinical Center W, Hauser, M.A., et al. A genome-wide association study of suicide attempts and suicidal ideation in U.S. military veterans. Psychiatry Res 269 (2018), 64–69.
16. Levey, D.F., Polimanti, R., Cheng, Z., Zhou, H., Nunez, Y.Z., Jain, S., et al. Genetic associations with suicide attempt severity and genetic overlap with major depression. Transl Psychiatry, 9(1), 2019, 22.
17. Li, J., Yoshikawa, A., Meltzer, H.Y., Replication of rs300774, a genetic biomarker near ACP1, associated with suicide attempts in patients with schizophrenia: Relation to brain cholesterol biosynthesis. J Psychiatr Res 94 (2017), 54–61.
18. Mullins, N., Perroud, N., Uher, R., Butler, A.W., Cohen-Woods, S., Rivera, M., et al. Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: a genome-wide association and polygenic scoring study. Am J Med Genet B Neuropsychiatr Genet 165B:5 (2014), 428–437.
19. Perlis, R.H., Huang, J., Purcell, S., Fava, M., Rush, A.J., Sullivan, P.F., et al. Genome-wide association study of suicide attempts in mood disorder patients. Am J Psychiatry 167:12 (2010), 1499–1507.
20. Perroud, N., Uher, R., Ng, M.Y., Guipponi, M., Hauser, J., Henigsberg, N., et al. Genome-wide association study of increasing suicidal ideation during antidepressant treatment in the GENDEP project. Pharmacogenomics J 12:1 (2012), 68–77.
21. Ruderfer, D.M., Fanous, A.H., Ripke, S., McQuillin, A., Amdur, R.L., Schizophrenia Working Group of Psychiatric Genomics C, et al. Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia. Mol Psychiatry 19:9 (2014), 1017–1024.
22. Stein, M.B., Ware, E.B., Mitchell, C., Chen, C.Y., Borja, S., Cai, T., et al. Genomewide association studies of suicide attempts in US soldiers. Am J Med Genet B Neuropsychiatr Genet 174:8 (2017), 786–797.
23. Willour, V.L., Seifuddin, F., Mahon, P.B., Jancic, D., Pirooznia, M., Steele, J., et al. A genome-wide association study of attempted suicide. Mol Psychiatry 17:4 (2012), 433–444.
24. Zai, C.C., Goncalves, V.F., Tiwari, A.K., Gagliano, S.A., Hosang, G., de Luca, V., et al. A genome-wide association study of suicide severity scores in bipolar disorder. J Psychiatr Res 65 (2015), 23–29.
25. Coon, H., Darlington, T.M., DiBlasi, E., Callor, W.B., Ferris, E., Fraser, A., et al. Genome-wide significant regions in 43 Utah high-risk families implicate multiple genes involved in risk for completed suicide. Mol Psychiatry, 2018, 10.1038/s41380-018-0282-3.
26. Erlangsen, A., Appadurai, V., Wang, Y., Turecki, G., Mors, O., Werge, T., et al. Genetics of suicide attempts in individuals with and without mental disorders: a population-based genome-wide association study. Mol Psychiatry, 2018, 10.1038/s41380-018-0218-y.
27. Ruderfer, D.M., Walsh, C.G., Aguirre, M.W., Tanigawa, Y., Ribeiro, J.D., Franklin, J.C., et al. Significant shared heritability underlies suicide attempt and clinically predicted probability of attempting suicide. Mol Psychiatry, 2019, 10.1038/s41380-018-0326-8.
28. Biobank, U.K., Genotype imputation and genetic association studies of UK Biobank, Interim data release. 11 September 2015 http://www.ukbiobank.ac.uk/wp-content/uploads/2014/04/imputation_documentation_May2015.pdf, 2015.
29. Biobank, U.K., Genotyping of 500,000 UK Biobank participants. Description of sample processing workflow and preparation of DNA for genotyping. 11 September 2015 https://biobank.ctsu.ox.ac.uk/crystal/docs/genotyping_sample_workflow.pdf, 2015.
30. Davis, K.A.S., Coleman, J.R.I., Adams, M., Allen, N., Breen, G., Cullen, B., et al. Mental health in UK Biobank: development, implementation and results from an online questionnaire completed by 157 366 participants. BJPsych Open 4:3 (2018), 83–90.
31. Christensen RHB, Ordinal - regression models for ordinal data. R package version, 2015 [6-28 ed2015].
32. Smith, D.J., Nicholl, B.I., Cullen, B., Martin, D., Ul-Haq, Z., Evans, J., et al. Prevalence and characteristics of probable major depression and bipolar disorder within UK biobank: cross-sectional study of 172,751 participants. PLoS One, 8(11), 2013, e75362.
33. Ng, Q.X., Yong, B.Z.J., Ho, C.Y.X., Lim, D.Y., Yeo, W.S., Early life sexual abuse is associated with increased suicide attempts: an update meta-analysis. J Psychiatr Res 99 (2018), 129–141.
34. Watanabe, K., Taskesen, E., van Bochoven, A., Posthuma, D., Functional mapping and annotation of genetic associations with FUMA. Nat Commun, 8(1), 2017, 1826.
35. Bulik-Sullivan, B., Finucane, H.K., Anttila, V., Gusev, A., Day, F.R., Loh, P.R., et al. An atlas of genetic correlations across human diseases and traits. Nat Genet 47:11 (2015), 1236–1241.
36. de Leeuw, C.A., Mooij, J.M., Heskes, T., Posthuma, D., MAGMA: generalized gene-set analysis of GWAS data. PLoS Comput Biol, 11(4), 2015, e1004219.
37. McLaren, W., Gil, L., Hunt, S.E., Riat, H.S., Ritchie, G.R., Thormann, A., et al. The ensembl variant effect predictor. Genome Biol, 17(1), 2016, 122.
38. Consortium, G.T., The Genotype-Tissue Expression (GTEx) project. Nat Genet 45:6 (2013), 580–585.
39. Oguro-Ando, A., Zuko, A., Kleijer, K.T.E., Burbach, J.P.H., A current view on contactin-4, −5, and −6: implications in neurodevelopmental disorders. Mol Cell Neurosci 81 (2017), 72–83.
40. Okbay, A., Baselmans, B.M., De Neve, J.E., Turley, P., Nivard, M.G., Fontana, M.A., et al. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nat Genet 48:6 (2016), 624–633.
41. Goes, F.S., McGrath, J., Avramopoulos, D., Wolyniec, P., Pirooznia, M., Ruczinski, I., et al. Genome-wide association study of schizophrenia in Ashkenazi Jews. Am J Med Genet B Neuropsychiatr Genet 168:8 (2015), 649–659.
42. Ward, J., Strawbridge, R.J., Bailey, M.E.S., Graham, N., Ferguson, A., Lyall, D.M., et al. Genome-wide analysis in UK Biobank identifies four loci associated with mood instability and genetic correlation with major depressive disorder, anxiety disorder and schizophrenia. Transl Psychiatry, 7(11), 2017, 1264.
43. Bernanke, J.A., Stanley, B.H., Oquendo, M.A., Toward fine-grained phenotyping of suicidal behavior: the role of suicidal subtypes. Mol Psychiatry 22:8 (2017), 1080–1081.
44. Wray, N.R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E.M., Abdellaoui, A., et al. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat Genet 50:5 (2018), 668–681.