Association study of 44 candidate genes with depressive and anxiety symptoms in post-partum women.
The post-partum period is a time of extreme vulnerability for a whole spectrum of psychiatric disorders. Delivery may be considered an important risk factor in genetically susceptible women. Five hundred and eight SNPs in 44 genes at candidate pathways putatively related to mood changes after delivery were genotyped in a multicenter cohort of 1804 women from Spain. Participants completed two scales at 2-3 days, 8 weeks, and 32 weeks post-partum, the Edinburgh Post-partum Depression Scale (EPDS) and the Spielberger State-Trait Anxiety Inventory (STAI). Those women who scored 9 or more on EPDS were evaluated for major depression using the Diagnostic Interview for Genetics Studies (DIGS) adapted for post-partum depression. Association with major depression was assessed using likelihood ratio tests under a codominant genotype model. Association with scale scores was tested using linear mixed models to take into account repeated measures over time. Two intronic SNPs, one at the serotonin transporter gene (SLC6A4) and another at dopa decarboxylase (DDC), were significantly associated to STAI anxiety scores after multiple testing correction (nominal P=0.0000513 and 0.000097, respectively). In addition, post hoc analysis at the unphased haplotype level using nominal significant SNPs revealed an association with a combination of three SNPs at protein kinase C, beta (PRKCB) with major depression, significant after multiple testing correction (nominal global P=0.0001596). In conclusion, we detected a role of SLC6A4 in mood changes after stressful events, and revealed new putative associations involving DDC and PRKCB. Therefore, these genes deserve further investigation to confirm these results.
Costas
Javier
J
Fundación Pública Galega de Medicina Xenómica-SERGAS, Hospital Clínico Universitario, Santiago de Compostela, Spain. javier.costas@usc.es
Gratacòs
Mònica
M
Escaramís
Geòrgia
G
Martín-Santos
Rocío
R
de Diego
Yolanda
Y
Baca-García
Enrique
E
Canellas
Francesca
F
Estivill
Xavier
X
Guillamat
Roser
R
Guitart
Miriam
M
Gutiérrez-Zotes
Alfonso
A
García-Esteve
Luisa
L
Mayoral
Fermín
F
Moltó
María Dolores
MD
Phillips
Christopher
C
Roca
Miquel
M
Carracedo
Angel
A
Vilella
Elisabet
E
Sanjuán
Julio
J
D001007:Anxiety / Q000235:genetics*; D015331:Cohort Studies; D019052:Depression, Postpartum / Q000235:genetics*; D004296:Dopa Decarboxylase / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D049590:Postpartum Period / Q000235:genetics* / Q000502:physiology / Q000523:psychology; D011493:Protein Kinase C / Q000235:genetics; D064546:Protein Kinase C beta; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013030:Spain; D013997:Time Factors; D044465:White People
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D004296:Dopa Decarboxylase