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Massachusetts General Hospital / Harvard Medical School

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Mol. Psychiatr., 07 April 2026 | https://doi.org/10.1038/s41380-026-03553-z Towards scalable biomarker discovery in posttraumatic stress disorder: triangulating genomic and phenotypic evidence from a health system biobank

Younga Heather Lee^1,2,3,4*, Yingzhe Zhang⁴, Ana Lucia Espinosa Dice⁴, Josephine H. Li^2,5,6,7, Justin D. Tubbs^2,3, Yen-Chen Anne Feng^2,3,8, Tian Ge^2,3,9, Adam X. Maihofer^10,11,12, Caroline M. Nievergelt^10,11,12, Jordan W. Smoller^2,3,9, Karestan C. Koenen^1,2,3,4,13, Andrea L. Roberts¹⁴ and Natalie Slopen^1,13*

¹Broad Trauma Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
²Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
³Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
⁴Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁵Diabetes Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁶Programs in Metabolism and Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
⁷Department of Medicine, Harvard Medical School, Boston, MA, USA.
⁸Institute of Health Data Analytics and Statistics, College of Public Health, National Taiwan University, Taipei, Taiwan.
⁹Center for Precision Psychiatry, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
¹⁰Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
¹¹Center of Excellence for Stress and Mental Health, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
¹²Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
¹³Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹⁴Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Corresponding authors
Correspondence to Younga Heather Lee or Natalie Slopen.

Abstract

Biomarkers can potentially improve the diagnosis, monitoring, and treatment of posttraumatic stress disorder (PTSD). However, PTSD biomarkers that are scalable and easily integrated into real-world clinical settings have not been identified. The analysis was conducted between June to November 2024 using genomic samples and laboratory test results recorded in the Mass General Brigham (MGB) Health System. The analysis included 23,743 European ancestry participants from the nested MGB Biobank study. The first exposure was polygenic risk score (PRS) for PTSD, calculated using the largest available European ancestry genome-wide association study (GWAS), employing a Bayesian polygenic scoring method. The second exposure was a clinical diagnosis of PTSD, determined by the presence of two or more instances of PTSD-related diagnostic codes in the longitudinal electronic health records (EHR). The primary outcomes were the inverse normal quantile transformed, median lab values of 241 laboratory traits with non-zero h2SNP estimates. Sixteen unique laboratory traits across the cardiometabolic, hematologic, hepatic, and immune systems were implicated in both genomic and phenotypic lab-wide association scans (LabWAS). Two-sample Mendelian randomization analyses provided evidence of potential unidirectional causal effects of PTSD liability on hepatic (decreased albumin and total bilirubin), cardiometabolic (decreased HDL cholesterol and increased VLDL cholesterol), and hematologic (decreased mean platelet volume) markers. These findings demonstrate the potential of a triangulation approach to uncover scalable and clinically relevant biomarkers for PTSD.

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외상 후 스트레스 장애 (Posttraumatic Stress Disorder [PTSD])는 보통 환자의 자기보고와 임상 면담 등 주관적 평가를 중심으로 진단됩니다. 이에 반해 이번 연구에서는 보다 객관적인 방법을 찾기 위해 혈액 검사 기반 바이오마커를 분석했습니다. 미국 매스 제너럴 브리검 의료 시스템의 약 2만 3천 명 데이터를 활용해, 다유전자 위험점수(Polygenic Risk Score [PRS]) 와 전자의무기록 기반 진단을 기준으로 241개의 혈액 지표를 분석했습니다. 그 결과, 알부민과 빌리루빈 같은 간 기능 지표 감소, HDL 감소와 VLDL 증가 같은 심혈관 지표 변화, 그리고 평균 혈소판 용적 감소 등이 PTSD 와 관련 있을 가능성을 확인했습니다.

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