Open AccessGenomics of posttraumatic stress disorder in veterans: Methods and rationale for V eterans A ffairs C ooperative S tudy #575B
Author(s) -
Radhakrishnan Krishnan,
Aslan Mihaela,
Harrington Kelly M.,
Pietrzak Robert H.,
Huang Grant,
Muralidhar Sumitra,
Cho Kelly,
Quaden Rachel,
Gag David,
Pyarajan Saiju,
Sun Ning,
Zhao Hongyu,
Gaziano Michael,
Concato John,
Stein Murray B.,
Gelernter Joel
Publication year - 2019
Publication title -
international journal of methods in psychiatric research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.275
H-Index - 73
eISSN - 1557-0657
pISSN - 1049-8931
DOI - 10.1002/mpr.1767
Subject(s) - veterans affairs , genome wide association study , posttraumatic stress , heritability , psychiatry , clinical psychology , medicine , statistical power , psychology , single nucleotide polymorphism , genetics , biology , statistics , mathematics , genotype , gene
Objectives Heritability in the risk for developing posttraumatic stress disorder (PTSD) has been established, but most genome‐wide association studies (GWASs) of PTSD involve relatively small sample sizes and limited identification of associated genetic loci. This report describes the methodology of a Veterans Affairs (VA) Cooperative Studies Program GWAS of PTSD among combat‐exposed U.S. veterans. Methods Probable cases (with PTSD) and probable controls (without PTSD) were identified from among veterans enrolled in the VA Million Veteran Program (MVP) with an algorithm developed using questionnaire responses and electronic health record information. This algorithm, based on a statistical model, relied on medical chart reviews as a reference standard and was refined using telephone interviews. Subsequently, to evaluate the impact of probabilistic phenotyping on statistical power, the threshold probability for case–control selection was varied in simulations. Results As of September 2018, >695,000 veterans have enrolled in MVP. For current analyses, genotyping data were available for >353,000 participants, including >83,000 combat‐exposed veterans. A threshold probability of 0.7 for case and control designation yielded an interim >16,000 cases and >33,000 controls. Conclusions A formal methodological approach was used to identify cases and controls for subsequent GWAS analyses to identify genetic risk loci for PTSD.