Relationship of Major Depressive Disorder and Schizophrenia Polygenic Risk Scores to Suicide: A Comparison Between European and Asian Ancestry Populations

Abstract

Psychiatric diagnosis rates in suicide decedents appear higher in European ancestry populations compared with East Asians. Shared genetic components exist between major depressive disorder (MDD)/schizophrenia (SCZ) and suicide, but no study has compared these shared polygenic architectures between Europeans and East Asians. We compared polygenic risk scores (PRSs) for MDD/SCZ determined from large data sets specific to each ancestry in European and East Asian suicide decedent samples. MDD/SCZ PRSs appeared more prominent in European suicides compared with Japanese suicides. A greater coexistence of psychiatric disorders in European suicide decedents than in East Asian suicide decedents may be partly explained by genetics. Our results are limited by the smaller sample size of our suicide decedents and sample size disparities between the European discovery data set and the East Asian data set for MDD/SCZ, resulting in less statistical power to detect robust difference between the two ancestries.

HIGHLIGHTS

• Psychiatric diagnosis in suicides appears more common in Europeans than in East Asians.

• This is the first comparison of suicide genome-wide association studies between Europeans and East Asians.

• Major depressive disorder/schizophrenia polygenic risk scores for suicide were more significant for Europeans than for East Asians.

Keywords:

• Multi-ethnicity
• polygenic risk score
• suicide

ACKNOWLEDGMENTS

We acknowledge the staff of the Biobank Japan (BBJ) project for collecting samples and clinical information, the staff of the RIKEN Center for Integrative Medical Sciences for genotyping and data management, and Dr. Toshiki Kono for statistical support.

DISCLOSURE STATEMENT

Dr. Mann receives royalties for commercial use of the C-SSRS from the Research Foundation for Mental Hygiene. Dr. Galfalvy and her family hold equity in Illumina, Inc. All other authors report no financial interests or potential conflicts of interest.

Additional information

Funding

This work was supported in part by SENSHIN Medical Research Foundation (to IO), JSPS KAKENHI Grant No. 21H02852/21K15712/20KK0194 (to AH and IO), Smoking Research Foundation (to AH), and NIMH Grant No. MH082041 (to JJM).

Notes on contributors

Ikuo Otsuka

Ikuo Otsuka, Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan, and Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.

Hanga Galfalvy

Hanga Galfalvy, Division of Molecular Imaging and Neuropathology, Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons and New York State Psychiatric Institute, New York, USA, and Department of Biostatistics, Columbia University Mailman School of Public Health, NY, USA.

Jia Guo

Jia Guo, Department of Biostatistics, Columbia University Mailman School of Public Health, New York, USA.

Masato Akiyama

Masato Akiyama, Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Satoshi Okazaki

Satoshi Okazaki, Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan.

Chikashi Terao

Chikashi Terao, Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.

Dan Rujescu

Dan Rujescu, Department of Psychiatry, Psychotherapy and Psychosomatics, Martin-Luther-University Halle-Wittenberg, Halle, Germany.

Gustavo Turecki

Gustavo Turecki, Douglas Institute, Department of Psychiatry, McGill University, Verdun, Quebec, Canada.

Akitoyo Hishimoto

Akitoyo Hishimoto, Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan.

J. John Mann

J. John Mann, Division of Molecular Imaging and Neuropathology, Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons and New York State Psychiatric Institute, New York, USA.