Re-testing reported significant SNPs related to suicide in a historical high -risk isolated population from north east India.
GWAS
Replication
SNPs
Suicide
Journal
Hereditas
ISSN: 1601-5223
Titre abrégé: Hereditas
Pays: England
ID NLM: 0374654
Informations de publication
Date de publication:
17 Jul 2020
17 Jul 2020
Historique:
received:
02
02
2020
accepted:
07
07
2020
entrez:
19
7
2020
pubmed:
19
7
2020
medline:
2
6
2021
Statut:
epublish
Résumé
Genetic diathesis of suicide is supported by family and twin studies. Few candidate gene pathways are known, but does not explain fully the complexity of suicide genetic risk. Recent investigations opting for Genome-Wide Association Studies (GWAS) resulted in finding additional targets, but replication remained a challenge. In this respect small isolated population approach in several complex disease phenotypes is found encouraging. The present study is an attempt to re-test some of the reported significant SNPs for suicide among a small historical high- risk isolated population from Northeast India. Two hundred ten cases (inclusive of depressed, suicide attempter and depressed + suicide attempter) and 249 controls were considered in the present study which were evaluated for the psychiatric parameters. Sixteen reported significant SNPs for suicide behaviour were re-tested using association approach under various genetic models. Networking by GeneMANIA tool was used for function prediction of the associated genes. Seven SNPs (of 6 genes) remained significant in different genetic models. On networking genes with significant SNPs IL7, RHEB, CTNN3, KCNIP4, ARFGEF3 are found in interaction with already known candidate gene pathways while SNP rs1109089 (RHEB) gained further support from earlier expression studies. NUGGC gene is in complete isolation. Small population approach in replicating significant SNPs is useful in complex phenotypes like suicide. This study explored the region-specific demographics of India by identifying vulnerable population for suicide via genetic association analysis in bringing into academic and administrative forum, the importance of suicide as a disease and its biological basis.
Sections du résumé
BACKGROUND
BACKGROUND
Genetic diathesis of suicide is supported by family and twin studies. Few candidate gene pathways are known, but does not explain fully the complexity of suicide genetic risk. Recent investigations opting for Genome-Wide Association Studies (GWAS) resulted in finding additional targets, but replication remained a challenge. In this respect small isolated population approach in several complex disease phenotypes is found encouraging. The present study is an attempt to re-test some of the reported significant SNPs for suicide among a small historical high- risk isolated population from Northeast India.
METHODS
METHODS
Two hundred ten cases (inclusive of depressed, suicide attempter and depressed + suicide attempter) and 249 controls were considered in the present study which were evaluated for the psychiatric parameters. Sixteen reported significant SNPs for suicide behaviour were re-tested using association approach under various genetic models. Networking by GeneMANIA tool was used for function prediction of the associated genes.
RESULTS
RESULTS
Seven SNPs (of 6 genes) remained significant in different genetic models. On networking genes with significant SNPs IL7, RHEB, CTNN3, KCNIP4, ARFGEF3 are found in interaction with already known candidate gene pathways while SNP rs1109089 (RHEB) gained further support from earlier expression studies. NUGGC gene is in complete isolation.
CONCLUSIONS
CONCLUSIONS
Small population approach in replicating significant SNPs is useful in complex phenotypes like suicide. This study explored the region-specific demographics of India by identifying vulnerable population for suicide via genetic association analysis in bringing into academic and administrative forum, the importance of suicide as a disease and its biological basis.
Identifiants
pubmed: 32680568
doi: 10.1186/s41065-020-00144-y
pii: 10.1186/s41065-020-00144-y
pmc: PMC7368720
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
31Références
Am J Med Genet B Neuropsychiatr Genet. 2014 Jul;165B(5):428-37
pubmed: 24964207
J Affect Disord. 2018 Jan 15;226:92-99
pubmed: 28968564
Am J Med Genet B Neuropsychiatr Genet. 2015 Oct;168(7):557-63
pubmed: 26079190
Mol Psychiatry. 2017 Sep;22(9):1250-1273
pubmed: 28809398
Transl Psychiatry. 2017 Sep 5;7(9):e1226
pubmed: 28872639
J Affect Disord. 2013 Nov;151(2):673-8
pubmed: 23978684
Front Psychiatry. 2016 Sep 23;7:158
pubmed: 27721799
Front Psychiatry. 2014 May 15;5:48
pubmed: 24860514
Transl Psychiatry. 2019 Jan 17;9(1):22
pubmed: 30655502
Nature. 2010 Oct 28;467(7319):1061-73
pubmed: 20981092
Brief Funct Genomics. 2014 Sep;13(5):371-7
pubmed: 25009120
Am J Hum Genet. 2007 Jul;81(1):17-31
pubmed: 17564960
Am J Psychiatry. 2019 Aug 1;176(8):651-660
pubmed: 31164008
PLoS One. 2018 Feb 15;13(2):e0192969
pubmed: 29447300
Am J Psychiatry. 2007 Sep;164(9):1364-70
pubmed: 17728421
Genome Biol. 2008;9(8):109
pubmed: 18771588
Biol Psychiatry. 2009 Apr 1;65(7):556-63
pubmed: 19201395
J Biol Chem. 2009 Oct 30;284(44):30652-61
pubmed: 19734146
Nature. 2014 Aug 14;512(7513):190-3
pubmed: 25043022
Neuropsychopharmacology. 2012 Feb;37(3):797-807
pubmed: 22030708
PLoS Genet. 2009 Feb;5(2):e1000365
pubmed: 19197348
Mol Psychiatry. 2016 Mar;21(3):313-9
pubmed: 26782056
Mol Psychiatry. 2012 Apr;17(4):433-44
pubmed: 21423239
Lancet Public Health. 2018 Oct;3(10):e459-e460
pubmed: 30219339
Crisis. 2017 Nov;38(6):367-375
pubmed: 28914095
PLoS One. 2011;6(7):e20690
pubmed: 21750702
F1000Res. 2018 May 24;7:
pubmed: 29899972
Pharmacogenomics J. 2012 Feb;12(1):68-77
pubmed: 20877300
Prim psychiatry. 2008 Jan 1;15(2):44-53
pubmed: 20354589
Transl Psychiatry. 2019 Dec 9;9(1):333
pubmed: 31819045
Curr Protoc Hum Genet. 2001 May;Chapter 9:Unit 9.8
pubmed: 18428319
Int J Environ Res Public Health. 2018 Jul 06;15(7):
pubmed: 29986446
J Biol Chem. 2012 Sep 14;287(38):31856-65
pubmed: 22833677
Am J Psychiatry. 2003 Aug;160(8):1486-93
pubmed: 12900312
Acta Psychiatr Scand. 2009 May;119(5):406-10
pubmed: 19367777
Behav Brain Res. 2016 Dec 15;315:147-9
pubmed: 27555535
Hum Mol Genet. 2002 Oct 1;11(20):2507-15
pubmed: 12351587
Am J Psychiatry. 2010 Dec;167(12):1499-507
pubmed: 21041247