Polygenic scores clarify the relationship between mental health and gender diversity

Thomas, Taylor R.; Tener, Ashton J.; Yang, Ji Seung; Strang, John; Michaelson, Jacob J.

doi:10.1101/2021.11.22.21266696

Cited by 6 publications

(4 citation statements)

References 65 publications

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“…Recent work suggests that gender identity diversity is associated with higher scores on a polygenic index created based on its ability to explain significant variance in cognitive performance, with greater gender diversity associated with polygenic scores predicting higher IQ. 70 This finding is relevant to studies examining diagnostic timing in autism given indications that autistic people with higher IQ tend to be diagnosed later relative to those with lower IQ. 54,71 Thus, examination of IQ, in addition to gender and gender diversity, is needed to fully understand differential patterns of diagnostic timing in autistic transgender and non-binary people.…”

Section: Discussionmentioning

confidence: 85%

Gender, assigned sex at birth, and gender diversity: Windows into diagnostic timing disparities in autism

McQuaid,

Ratto,

Jack

et al. 2024

Autism

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Later autism diagnosis is associated with increased mental health risks. Understanding disparities in diagnostic timing is important to reduce psychiatric burden for autistic people. One characteristic associated with later autism diagnosis is female sex assigned at birth. However, literature to date does not characterize, differentiate, or account for gender identity beyond assigned sex at birth. Gender diversity may be more common in autistic relative to neurotypical people, and autism is proportionally overrepresented in gender-diverse populations. We examined age at autism diagnosis by assigned sex at birth, gender identity, and gender diversity (gender-diverse vs cisgender) status, separately. Three independent cohorts representing different ascertainments were examined: a research-recruited academic medical center sample ( N = 193; 8.0–18.0 years); a clinic-based sample ( N = 1550; 1.3–25.4 years); and a community-enriched sample ( N = 244, 18.2–30.0 years). The clinic-based and community-enriched samples revealed disparities in diagnostic timing: people assigned female at birth, people of female gender, and gender-diverse people were diagnosed with autism significantly later than persons assigned male at birth, persons of male gender, and cisgender persons, respectively. Birth-sex, gender identity, and gender diversity may each uniquely relate to disparities in autism diagnostic timing. The influence of ascertainment strategies, particularly in studies examining assigned sex at birth or gender identity, should be considered. Lay Abstract Later autism diagnosis is associated with risk for mental health problems. Understanding factors related to later autism diagnosis may help reduce mental health risks for autistic people. One characteristic associated with later autism diagnosis is female sex. However, studies often do not distinguish sex assigned at birth and gender identity. Gender diversity may be more common in autistic relative to neurotypical people, and autism is more common in gender-diverse populations. We studied age at autism diagnosis by sex assigned at birth, gender identity, and gender diversity (gender-diverse vs cisgender) status, separately. We studied three separate autistic samples, each of which differed in how they were diagnosed and how they were recruited. The samples included 193 persons (8.0–18.0 years) from a research-recruited academic medical center sample; 1,550 people (1.3–25.4 years) from a clinic-based sample; and 244 people (18.2–30.0 years) from a community-enriched sample. We found significant differences in the clinic-based and community-enriched samples. People assigned female sex at birth were diagnosed with autism significantly later than people assigned male at birth. People of female gender were diagnosed significantly later than people of male gender. Gender-diverse people were diagnosed significantly later than cisgender people. Sex assigned at birth, gender identity, and gender diversity may each show unique relationships with age of autism diagnosis. Differences in how autistic people are diagnosed and recruited are important to consider in studies that examine sex assigned at birth or gender identity. More research into autism diagnosis in adulthood is needed.

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Section: Discussionmentioning

confidence: 85%

Gender, assigned sex at birth, and gender diversity: Windows into diagnostic timing disparities in autism

McQuaid,

Ratto,

Jack

et al. 2024

Autism

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“…Further, discrete categories may miss the nuance of experienced gender in the population. For example, the continuum-based values also capture meaningful gender variability for cisgender individuals, which has been linked to polygenic propensity variation (Thomas et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

The Gender Self-Report: A multidimensional gender characterization tool for gender-diverse and cisgender youth and adults.

Strang¹,

Wallace²,

Michaelson³

et al. 2023

American Psychologist

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Gender identity is a core component of human experience, critical to account for in broad health, development, psychosocial research, and clinical practice. Yet, the psychometric characterization of gender has been impeded due to challenges in modeling the myriad gender self-descriptors, statistical power limitations related to multigroup analyses, and equity-related concerns regarding the accessibility of complex gender terminology. Therefore, this initiative employed an iterative multi-community-driven process to develop the Gender Self-Report (GSR), a multidimensional gender characterization tool, accessible to youth and adults, nonautistic and autistic people, and gender-diverse and cisgender individuals. In Study 1, the GSR was administered to 1,654 individuals, sampled through seven diversified recruitments to be representative across age (10–77 years), gender and sexuality diversity (∼33% each gender diverse, cisgender sexual minority, cisgender heterosexual), and autism status (>33% autistic). A random half-split subsample was subjected to exploratory factor analytics, followed by confirmatory analytics in the full sample. Two stable factors emerged: Nonbinary Gender Diversity and Female–Male Continuum (FMC). FMC was transformed to Binary Gender Diversity based on designated sex at birth to reduce collinearity with designated sex at birth. Differential item functioning by age and autism status was employed to reduce item–response bias. Factors were internally reliable. Study 2 demonstrated the construct, convergent, and ecological validity of GSR factors. Of the 30 hypothesized validation comparisons, 26 were confirmed. The GSR provides a community-developed gender advocacy tool with 30 self-report items that avoid complex gender-related “insider” language and characterize diverse populations across continuous multidimensional binary and nonbinary gender traits.

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“…Much of this methodology has been previously described in our prior work [28]. We describe a few small updates to our methodology and ensured we followed current best practices with the PGS calculation tool used here.…”

Section: Genetic Data and Polygenic Score Analysismentioning

confidence: 99%

Lingo: an automated, web-based deep phenotyping platform for language ability

Casten,

Koomar,

Elsadany

et al. 2024

Preprint

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Background: Language and the ability to communicate effectively are key factors in mental health and well-being. Despite this critical importance, research on language is limited by the lack of a scalable phenotyping toolkit. Methods: Here, we describe and showcase Lingo - a flexible online battery of language and nonverbal reasoning skills based on seven widely used tasks (COWAT, picture narration, vocal rhythm entrainment, rapid automatized naming, following directions, sentence repetition, and nonverbal reasoning). The current version of Lingo takes approximately 30 minutes to complete, is entirely open source, and allows for a wide variety of performance metrics to be extracted. We asked > 1,300 individuals from multiple samples to complete Lingo, then investigated the validity and utility of the resulting data. Results: We conducted an exploratory factor analysis across 14 features derived from the seven assessments, identifying five factors. Four of the five factors showed acceptable test-retest reliability (Pearson's R > 0.7). Factor 2 showed the highest reliability (Pearson's R = 0.95) and loaded primarily on sentence repetition task performance. We validated Lingo with objective measures of language ability by comparing performance to gold-standard assessments: CELF-5 and the VABS-3. Factor 2 was significantly associated with the CELF-5 "core language ability" scale (Pearson's R = 0.77, p-value < 0.05) and the VABS-3 "communication" scale (Pearson's R = 0.74, p value < 0.05). Factor 2 was positively associated with phenotypic and genetic measures of socieconomic status. Interestingly, we found the parents of children with language impairments had lower Factor 2 scores (p-value < 0.01). Finally, we found Lingo factor scores were significantly predictive of numerous psychiatric and neurodevelopmental conditions. Conclusions: Together, these analyses support Lingo as a powerful platform for scalable deep phenotyping of language and other cognitive abilities. Additionally, exploratory analyses provide supporting evidence for the heritability of language ability and the complex relationship between mental health and language.

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Polygenic scores clarify the relationship between mental health and gender diversity

Cited by 6 publications

References 65 publications

Gender, assigned sex at birth, and gender diversity: Windows into diagnostic timing disparities in autism

Gender, assigned sex at birth, and gender diversity: Windows into diagnostic timing disparities in autism

The Gender Self-Report: A multidimensional gender characterization tool for gender-diverse and cisgender youth and adults.

Lingo: an automated, web-based deep phenotyping platform for language ability

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