RGD Reference Report - Mutation burden analysis of six common mental disorders in African Americans by whole genome sequencing. - Rat Genome Database

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Mutation burden analysis of six common mental disorders in African Americans by whole genome sequencing.

Authors: Liu, Yichuan  Qu, Hui-Qi  Chang, Xiao  Qu, Jingchun  Mentch, Frank D  Nguyen, Kenny  Tian, Lifeng  Glessner, Joseph  Sleiman, Patrick M A  Hakonarson, Hakon 
Citation: Liu Y, etal., Hum Mol Genet. 2022 Nov 10;31(22):3769-3776. doi: 10.1093/hmg/ddac129.
RGD ID: 401854249
Pubmed: PMID:35642741   (View Abstract at PubMed)
DOI: DOI:10.1093/hmg/ddac129   (Journal Full-text)

Mental disorders present a global health concern and have limited treatment options. In today's medical practice, medications such as antidepressants are prescribed not only for depression but also for conditions such as anxiety and attention deficit hyperactivity disorder (ADHD). Therefore, identifying gene targets for specific disorders is important and offers improved precision. In this study, we performed a genetic analysis of six common mental disorders-ADHD, anxiety, depression, delays in mental development, intellectual disabilities (IDs) and speech/language disorder-in the ethnic minority of African Americans (AAs) using whole genome sequencing (WGS). WGS data were generated from blood-derived DNA from 4178 AA individuals, including 1384 patients with the diagnosis of at least one mental disorder. Mutation burden analysis was applied based on rare and deleterious mutations in the AA population between cases and controls, and further analyzed in the context of patients with single mental disorder diagnosis. Certain genes uncovered demonstrated significant P-values in mutation burden analysis. In addition, exclusive recurrences in specific type of disorder were scanned through gene-drug interaction databases to assess for availability of potential medications. We uncovered 15 genes harboring deleterious mutations, including 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR) and Uronyl 2-Sulfotransferase (UST) for ADHD; Farnesyltransferase, CAAX Box, Beta (FNTB) for anxiety; Xin Actin Binding Repeat Containing 2 (XIRP2), Natriuretic Peptide C (NPPC), Serine/Threonine Kinase 33 (STK33), Pannexin 1 (PANX1) and Neurotensin (NTS) for depression; RUNX Family Transcription Factor 3 (RUNX3), Tachykinin Receptor 1 (TACR1) and NADH:Ubiquinone Oxidoreductase Core Subunit S7 (NDUFS7) for delays in mental development; Hepsin (HPN) for ID and Collagen Type VI Alpha 3 Chain (COL6A3), Damage Specific DNA Binding Protein 1 (DDB1) and NADH:Ubiquinone Oxidoreductase Subunit A11 (NDUFA11) for speech/language disorder. Taken together, we have established critical insights into the development of new precision medicine approaches for mental disorders in AAs.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FNTBHumananxiety disorder  IAGP DNA:SNP:CDS:multiple (human)RGD 
FntbRatanxiety disorder  ISOFNTB (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
FntbMouseanxiety disorder  ISOFNTB (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
HMGCRHumanattention deficit hyperactivity disorder  IAGP DNA:SNP:CDS:mutiple (human)RGD 
HmgcrRatattention deficit hyperactivity disorder  ISOHMGCR (Homo sapiens)DNA:SNP:CDS:mutiple (human)RGD 
HmgcrMouseattention deficit hyperactivity disorder  ISOHMGCR (Homo sapiens)DNA:SNP:CDS:mutiple (human)RGD 
USTHumanattention deficit hyperactivity disorder  IAGP DNA:SNP:CDS:mutiple (human)RGD 
UstRatattention deficit hyperactivity disorder  ISOUST (Homo sapiens)DNA:SNP:CDS:mutiple (human)RGD 
UstMouseattention deficit hyperactivity disorder  ISOUST (Homo sapiens)DNA:SNP:CDS:mutiple (human)RGD 
COL6A3Humancommunication disorder  IAGP DNA:SNP:CDS:multiple (human)RGD 
Col6a3Ratcommunication disorder  ISOCOL6A3 (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
Col6a3Mousecommunication disorder  ISOCOL6A3 (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
DDB1Humancommunication disorder  IAGP DNA:SNP:CDS:multiple (human)RGD 
Ddb1Ratcommunication disorder  ISODDB1 (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
Ddb1Mousecommunication disorder  ISODDB1 (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
NDUFA11Humancommunication disorder  IAGP DNA:SNP:CDS:multiple (human)RGD 
Ndufa11Ratcommunication disorder  ISONDUFA11 (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
Ndufa11Mousecommunication disorder  ISONDUFA11 (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
NPPCHumandepressive disorder  IAGP DNA:SNP:CDS:multiple (human)RGD 
NTSHumandepressive disorder  IAGP DNA:SNP:CDS:multiple (human)RGD 
NppcRatdepressive disorder  ISONPPC (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
NppcMousedepressive disorder  ISONPPC (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
NtsRatdepressive disorder  ISONTS (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
NtsMousedepressive disorder  ISONTS (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
PANX1Humandepressive disorder  IAGP DNA:SNP:CDS:multiple (human)RGD 
Panx1Ratdepressive disorder  ISOPANX1 (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
Panx1Mousedepressive disorder  ISOPANX1 (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
STK33Humandepressive disorder  IAGP DNA:SNP:CDS:multiple (human)RGD 
Stk33Mousedepressive disorder  ISOSTK33 (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
Stk33Ratdepressive disorder  ISOSTK33 (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
XIRP2Humandepressive disorder  IAGP DNA:SNP:CDS:multiple (human)RGD 
Xirp2Ratdepressive disorder  ISOXIRP2 (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
Xirp2Mousedepressive disorder  ISOXIRP2 (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
NDUFS7Humandevelopmental disorder of mental health  IAGP DNA:SNP:CDS:multiple (human)RGD 
Ndufs7Ratdevelopmental disorder of mental health  ISONDUFS7 (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
Ndufs7Mousedevelopmental disorder of mental health  ISONDUFS7 (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
RUNX3Humandevelopmental disorder of mental health  IAGP DNA:SNP:CDS:multiple (human)RGD 
Runx3Ratdevelopmental disorder of mental health  ISORUNX3 (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
Runx3Mousedevelopmental disorder of mental health  ISORUNX3 (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
TACR1Humandevelopmental disorder of mental health  IAGP DNA:SNP:CDS:multiple (human)RGD 
Tacr1Ratdevelopmental disorder of mental health  ISOTACR1 (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
Tacr1Mousedevelopmental disorder of mental health  ISOTACR1 (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
HPNHumanintellectual disability  IAGP DNA:SNP:CDS:multiple (human)RGD 
HpnRatintellectual disability  ISOHPN (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 
HpnMouseintellectual disability  ISOHPN (Homo sapiens)DNA:SNP:CDS:multiple (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Col6a3  (collagen type VI alpha 3 chain)
Ddb1  (damage-specific DNA binding protein 1)
Fntb  (farnesyltransferase, CAAX box, subunit beta)
Hmgcr  (3-hydroxy-3-methylglutaryl-CoA reductase)
Hpn  (hepsin)
Ndufa11  (NADH:ubiquinone oxidoreductase subunit A11)
Ndufs7  (NADH:ubiquinone oxidoreductase core subunit S7)
Nppc  (natriuretic peptide C)
Nts  (neurotensin)
Panx1  (Pannexin 1)
Runx3  (RUNX family transcription factor 3)
Stk33  (serine/threonine kinase 33)
Tacr1  (tachykinin receptor 1)
Ust  (uronyl-2-sulfotransferase)
Xirp2  (xin actin-binding repeat containing 2)

Genes (Mus musculus)
Col6a3  (collagen, type VI, alpha 3)
Ddb1  (damage specific DNA binding protein 1)
Fntb  (farnesyltransferase, CAAX box, beta)
Hmgcr  (3-hydroxy-3-methylglutaryl-Coenzyme A reductase)
Hpn  (hepsin)
Ndufa11  (NADH:ubiquinone oxidoreductase subunit A11)
Ndufs7  (NADH:ubiquinone oxidoreductase core subunit S7)
Nppc  (natriuretic peptide type C)
Nts  (neurotensin)
Panx1  (pannexin 1)
Runx3  (runt related transcription factor 3)
Stk33  (serine/threonine kinase 33)
Tacr1  (tachykinin receptor 1)
Ust  (uronyl-2-sulfotransferase)
Xirp2  (xin actin-binding repeat containing 2)

Genes (Homo sapiens)
COL6A3  (collagen type VI alpha 3 chain)
DDB1  (damage specific DNA binding protein 1)
FNTB  (farnesyltransferase, CAAX box, subunit beta)
HMGCR  (3-hydroxy-3-methylglutaryl-CoA reductase)
HPN  (hepsin)
NDUFA11  (NADH:ubiquinone oxidoreductase subunit A11)
NDUFS7  (NADH:ubiquinone oxidoreductase core subunit S7)
NPPC  (natriuretic peptide C)
NTS  (neurotensin)
PANX1  (pannexin 1)
RUNX3  (RUNX family transcription factor 3)
STK33  (serine/threonine kinase 33)
TACR1  (tachykinin receptor 1)
UST  (uronyl 2-sulfotransferase)
XIRP2  (xin actin binding repeat containing 2)


Additional Information