Genome-wide association study implicates a novel RNA gene, the lincRNA AC068718.1, as a risk factor for post-traumatic stress disorder in women.
Posttraumatic stress disorder (PTSD) is a common and debilitating mental disorder with a particularly high burden for women. Emerging evidence suggests PTSD may be more heritable among women and evidence from animal models and human correlational studies suggest connections between sex-linked biology and PTSD vulnerability, which may extend to the disorder's genetic architecture. We conducted a genome-wide association study (GWAS) of PTSD in a primarily African American sample of women from the Detroit Neighborhood Health Study (DNHS) and tested for replication in an independent cohort of primarily European American women from the Nurses Health Study II (NHSII). We genotyped 413 DNHS women - 94 PTSD cases and 319 controls exposed to at least one traumatic event - on the Illumina HumanOmniExpress BeadChip for >700,000 markers and tested 578 PTSD cases and 1963 controls from NHSII for replication. We performed a network-based analysis integrating data from GWAS-derived independent regions of association and the Reactome database of functional interactions. We found genome-wide significant association for one marker mapping to a novel RNA gene, lincRNA AC068718.1, for which we found suggestive evidence of replication in NHSII. Our network-based analysis indicates that our top GWAS results were enriched for pathways related to telomere maintenance and immune function. Our findings implicate a novel RNA gene, lincRNA AC068718.1, as risk factor for PTSD in women and add to emerging evidence that non-coding RNA genes may play a crucial role in shaping the landscape of gene regulation with putative pathological effects that lead to phenotypic differences.
Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, NY, USA.
Guia
G
Guffanti
Sandro
S
Galea
Lulu
L
Yan
Andrea L
AL
Roberts
Nadia
N
Solovieff
Allison E
AE
Aiello
Jordan W
JW
Smoller
Immaculata
I
De Vivo
Hardeep
H
Ranu
Monica
M
Uddin
Derek E
DE
Wildman
Shaun
S
Purcell
Karestan C
KC
Koenen
D001741:Black or African American; D016022:Case-Control Studies; D004522:Educational Status; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D017533:Marital Status; D008824:Michigan / Q000453:epidemiology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012313:RNA / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D012307:Risk Factors; D012959:Socioeconomic Factors; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics* / Q000523:psychology
D062085:RNA, Long Noncoding; D012313:RNA
GWAS; Immune system; PTSD; Telomere maintenance; lincRNA