Identification of 15 genetic loci associated with risk of major depression in individuals of European descent

Nature Genetics

Volumn 48, Issue 9, 2016, Pages 1031-1036

  Hyde, Craig L ^a   Nagle, Michael W ^a   Tian, Chao ^b   Chen, Xing ^a   Paciga, Sara A ^a   Wendland, Jens R ^a   Tung, Joyce Y ^b   Hinds, David A ^b   Perlis, Roy H ^c   Winslow, Ashley R ^a,d  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United States)

^b 23 and Me Inc ^*  (United States)

^c MASSACHUSETTS GENERAL HOSPITAL   (United States)

^d UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADOLESCENT; ADULT; AGE DISTRIBUTION; AGED; ALZHEIMER DISEASE; ARTICLE; BIPOLAR DISORDER; DEGENERATIVE DISEASE; DEPRESSION; DISEASE ASSOCIATION; DNA FLANKING REGION; EUROPEAN; FEMALE; GENE EXPRESSION; GENE FREQUENCY; GENE IDENTIFICATION; GENE LINKAGE DISEQUILIBRIUM; GENE LOCUS; GENE REPLICATION; GENETIC RISK; GENETIC SUSCEPTIBILITY; GENOME-WIDE ASSOCIATION STUDY; GENOMICS; GENOTYPE; HAPLOTYPE; HERITABILITY; HUMAN; MAJOR DEPRESSION; MALE; META ANALYSIS; NERVOUS SYSTEM DEVELOPMENT; NEUROSIS; NORMAL HUMAN; ONSET AGE; PARKINSON DISEASE; PHENOTYPE; PLEIOTROPY; PRIORITY JOURNAL; PROGENY; QUANTITATIVE TRAIT LOCUS; SCHIZOPHRENIA; SELF REPORT; SEX DIFFERENCE; SINGLE NUCLEOTIDE POLYMORPHISM; Y CHROMOSOME; CASE CONTROL STUDY; CAUCASIAN; COMPARATIVE STUDY; GENETIC PREDISPOSITION; GENETICS; META ANALYSIS (TOPIC); MIDDLE AGED; RISK FACTOR;

ADULT; CASE-CONTROL STUDIES; DEPRESSIVE DISORDER, MAJOR; EUROPEAN CONTINENTAL ANCESTRY GROUP; FEMALE; GENETIC LOCI; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HUMANS; MALE; META-ANALYSIS AS TOPIC; MIDDLE AGED; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE; RISK FACTORS;

EID: 84980347551     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/ng.3623     Document Type: Article

References (36)

1. Angst, F., Stassen, H.H., Clayton, P.J. & Angst, J. Mortality of patients with mood disorders: follow-up over 34-38 years. J. Affect. Disord. 68, 167-181 (2002).
2. Lopez, A.D., Mathers, C.D., Ezzati, M., Jamison, D.T. & Murray, C.J. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 367, 1747-1757 (2006).
3. Wittchen, H.U. et al. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur. Neuropsychopharmacol. 21, 655-679 (2011).
4. Lichtenstein, P. et al. Recurrence risks for schizophrenia in a Swedish national cohort. Psychol. Med. 36, 1417-1425 (2006).
5. Sullivan, P.F., Kendler, K.S. & Neale, M.C. Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch. Gen. Psychiatry 60, 1187-1192 (2003).
6. CONVERGE Consortium. Sparse whole-genome sequencing identifes two loci for major depressive disorder. Nature 523, 588-591 (2015).
7. Hawrylycz, M.J. et al. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature 489, 391-399 (2012).
8. Le Meur, N. et al. MEF2C haploinsuffciency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations. J. Med. Genet. 47, 22-29 (2010).
9. Paciorkowski, A.R. et al. MEF2C haploinsuffciency features consistent hyperkinesis, variable epilepsy, and has a role in dorsal and ventral neuronal developmental pathways. Neurogenetics 14, 99-111 (2013).
10. Barbosa, A.C. et al. MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and function. Proc. Natl. Acad. Sci. USA 105, 9391-9396 (2008).
11. Wilkinson, M.B. et al. Imipramine treatment and resiliency exhibit similar chromatin regulation in the mouse nucleus accumbens in depression models. J. Neurosci. 29, 7820-7832 (2009).
12. Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421-427 (2014).
13. Cross-Disorder Group of the Psychiatric Genomics Consortium. Identifcation of risk loci with shared effects on fve major psychiatric disorders: a genome-wide analysis. Lancet 381, 1371-1379 (2013).
14. Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium. A mega-analysis of genome-wide association studies for major depressive disorder. Mol. Psychiatry 18, 497-511 (2013).
15. Whitehead, A. Meta-Analysis of Controlled Clinical Trials (John Wiley & Sons, 2002).
16. Agoston, Z. et al. Meis2 is a Pax6 co-factor in neurogenesis and dopaminergic periglomerular fate specifcation in the adult olfactory bulb. Development 141, 28-38 (2014).
17. Agoston, Z., Li, N., Haslinger, A., Wizenmann, A. & Schulte, D. Genetic and physical interaction of Meis2, Pax3 and Pax7 during dorsal midbrain development. BMC Dev. Biol. 12, 10 (2012).
18. Pers, T.H. et al. Biological interpretation of genome-wide association studies using predicted gene functions. Nat. Commun. 6, 5890 (2015).
19. Purcell, S., Cherny, S.S. & Sham, P.C. Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics 19, 149-150 (2003).
20. Bulik-Sullivan, B.K. et al. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat. Genet. 47, 291-295 (2015).
21. Okbay, A. et al. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identifed through genome-wide analyses. Nat. Genet. 48, 624-633 (2016).
22. Psychiatric GWAS Consortium Bipolar Disorder Working Group. Large-scale genome-wide association analysis of bipolar disorder identifes a new susceptibility locus near ODZ4. Nat. Genet. 43, 977-983 (2011).
23. Keller, M.B. et al. Results of the DSM-IV mood disorders feld trial. Am. J. Psychiatry 152, 843-849 (1995).
24. Regier, D.A. et al. DSM-5 feld trials in the United States and Canada, Part II: test-retest reliability of selected categorical diagnoses. Am. J. Psychiatry 170, 59-70 (2013).
25. Wisniewski, S.R. et al. Can phase III trial results of antidepressant medications be generalized to clinical practice? A STAR∗D report. Am. J. Psychiatry 166, 599-607 (2009).
26. Castro, V.M. et al. Validation of electronic health record phenotyping of bipolar disorder cases and controls. Am. J. Psychiatry 172, 363-372 (2015).
27. Eriksson, N. et al. Web-based, participant-driven studies yield novel genetic associations for common traits. PLoS Genet. 6, e1000993 (2010).
28. Tung, J.Y. et al. Effcient replication of over 180 genetic associations with self-reported medical data. PLoS One 6, e23473 (2011).
29. 1000 Genomes Project Consortium. An integrated map of genetic variation from 1, 092 human genomes. Nature 491, 56-65 (2012).
30. Browning, S.R. & Browning, B.L. Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering. Am. J. Hum. Genet. 81, 1084-1097 (2007).
31. Fuchsberger, C., Abecasis, G.R. & Hinds, D.A. minimac2: faster genotype imputation. Bioinformatics 31, 782-784 (2015).
32. Durand, E.Y., Do, C.B., Mountain, J.L. & Macpherson, J.M. Ancestry Composition: a novel, effcient pipeline for ancestry deconvolution. Preprint at bioRxiv http://dx.doi.org/10.1101/010512 (2014).
33. Henn, B.M. et al. Cryptic distant relatives are common in both isolated and cosmopolitan genetic samples. PLoS One 7, e34267 (2012).
34. Lehoucq, R.B., Sorensen, D.C. & Yang, C. ARPACK Users' Guide: Solution of Large-Scale Eigenvalue Problems with Implicitly Restarted Arnoldi Methods (SIAM, 1998).
35. Tucker, G., Price, A.L. & Berger, B. Improving the power of GWAS and avoiding confounding from population stratifcation with PC-Select. Genetics 197, 1045-1049 (2014).
36. Fehrmann, R.S. et al. Gene expression analysis identifes global gene dosage sensitivity in cancer. Nat. Genet. 47, 115-125 (2015).