Polygenic scores clarify the relationship between mental health and gender diversity

Taylor R. Thomas; Ashton J. Tener; Amy M. Pearlman; Katherine L. Imborek; Ji Seung Yang; John F. Strang; Jacob J. Michaelson

doi:10.1016/j.bpsgos.2024.100291

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Polygenic scores clarify the relationship between mental health and gender diversity

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Polygenic scores clarify the relationship between mental health and gender diversity

Taylor R. Thomas, Ashton J. Tener, Amy M. Pearlman, Katherine L. Imborek, Ji Seung Yang, John F. Strang and Jacob J. Michaelson

Biological psychiatry global open science, Vol.4(2), 100291

03/2024

DOI: 10.1016/j.bpsgos.2024.100291

PMCID: PMC10901838

PMID: 38425476

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Abstract

BACKGROUND: Gender diverse individuals are at increased risk for mental health problems, but it is unclear whether this is due to shared environmental or genetic factors. METHODS: In two SPARK samples, we tested for associations of 16 polygenic scores (PGS) with quantitative measures of gender diversity and mental health. In Study 1, 𝑁 = 639 independent adults (59% autistic) reported their mental health with the Adult Self Report (ASR) and their gender diversity with the Gender Self Report (GSR). The GSR has two dimensions: Binary (degree of identification with the gender opposite that implied by sex designated at birth) and Nonbinary (degree of identification with a gender that is neither male nor female). In Study 2 (𝑁 = 5,165), we used categorical gender identity. RESULTS: In Study 1, neuropsychiatric PGS were positively associated with ASR scores: Externalizing was positively associated with ADHD PGS (𝛽 = 0.10[0.03,0.17]) and Internalizing with PGS for depression (𝛽 = 0.07[0,0.14]) and neuroticism (𝛽 = 0.10[0.03,0.17]). Interestingly, GSR scores were not significantly associated with any neuropsychiatric PGS. However, GSR Nonbinary was positively associated with cognitive performance PGS (𝛽 = 0.11[0.05,0.18]), with the effect size comparable in magnitude to the neuropsychiatric PGS associations with the ASR. Additionally, GSR Binary was positively associated with non-heterosexual sexual behavior PGS (𝛽 = 0.07[0,0.14]). In Study 2, the cognitive performance PGS effect replicated; transgender and nonbinary individuals had higher PGS (𝑡 = 4.16). CONCLUSIONS: We show that while gender diversity is phenotypically positively associated with mental health problems, the strongest PGS associations with gender diversity were cognitive performance PGS, not neuropsychiatric PGS.

Details

Title: Subtitle: Polygenic scores clarify the relationship between mental health and gender diversity
Creators: Taylor R. Thomas - University of Iowa
Ashton J. Tener - University of Iowa
Amy M. Pearlman - University of Iowa
Katherine L. Imborek - University of Iowa
Ji Seung Yang - University of Maryland, College Park
John F. Strang - George Washington University
Jacob J. Michaelson - University of Iowa
Resource Type: Journal article
Publication Details: Biological psychiatry global open science, Vol.4(2), 100291
DOI: 10.1016/j.bpsgos.2024.100291
PMID: 38425476
PMCID: PMC10901838
NLM abbreviation: Biol Psychiatry Glob Open Sci
ISSN: 2667-1743
eISSN: 2667-1743
Language: English
Electronic publication date: 01/2024
Date published: 03/2024
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Communication Sciences and Disorders; Psychiatry; Iowa Neuroscience Institute; Family and Community Medicine
Record Identifier: 9984555560202771

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