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The sexual brain, genes, and cognition: A machine‐predicted brain sex score explains individual differences in cognitive intelligence and genetic influence in young children

Sex impacts the development of the brain and cognition differently across individuals. However, the literature on brain sex dimorphism in humans is mixed. We aim to investigate the biological underpinnings of the individual variability of sexual dimorphism in the brain and its impact on cognitive pe...

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Autores principales: Kim, Kakyeong, Joo, Yoonjung Yoonie, Ahn, Gun, Wang, Hee‐Hwan, Moon, Seo‐Yoon, Kim, Hyeonjin, Ahn, Woo‐Young, Cha, Jiook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294341/
https://www.ncbi.nlm.nih.gov/pubmed/35471639
http://dx.doi.org/10.1002/hbm.25888
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author Kim, Kakyeong
Joo, Yoonjung Yoonie
Ahn, Gun
Wang, Hee‐Hwan
Moon, Seo‐Yoon
Kim, Hyeonjin
Ahn, Woo‐Young
Cha, Jiook
author_facet Kim, Kakyeong
Joo, Yoonjung Yoonie
Ahn, Gun
Wang, Hee‐Hwan
Moon, Seo‐Yoon
Kim, Hyeonjin
Ahn, Woo‐Young
Cha, Jiook
author_sort Kim, Kakyeong
collection PubMed
description Sex impacts the development of the brain and cognition differently across individuals. However, the literature on brain sex dimorphism in humans is mixed. We aim to investigate the biological underpinnings of the individual variability of sexual dimorphism in the brain and its impact on cognitive performance. To this end, we tested whether the individual difference in brain sex would be linked to that in cognitive performance that is influenced by genetic factors in prepubertal children (N = 9,658, ages 9–10 years old; the Adolescent Brain Cognitive Development study). To capture the interindividual variability of the brain, we estimated the probability of being male or female based on the brain morphometry and connectivity features using machine learning (herein called a brain sex score). The models accurately classified the biological sex with a test ROC–AUC of 93.32%. As a result, a greater brain sex score correlated significantly with greater intelligence (p (fdr) < .001, [Formula: see text]  = .011–.034; adjusted for covariates) and higher cognitive genome‐wide polygenic scores (GPSs) (p (fdr) < .001, [Formula: see text]  < .005). Structural equation models revealed that the GPS‐intelligence association was significantly modulated by the brain sex score, such that a brain with a higher maleness score (or a lower femaleness score) mediated a positive GPS effect on intelligence (indirect effects = .006–.009; p = .002–.022; sex‐stratified analysis). The finding of the sex modulatory effect on the gene–brain–cognition relationship presents a likely biological pathway to the individual and sex differences in the brain and cognitive performance in preadolescence.
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spelling pubmed-92943412022-07-20 The sexual brain, genes, and cognition: A machine‐predicted brain sex score explains individual differences in cognitive intelligence and genetic influence in young children Kim, Kakyeong Joo, Yoonjung Yoonie Ahn, Gun Wang, Hee‐Hwan Moon, Seo‐Yoon Kim, Hyeonjin Ahn, Woo‐Young Cha, Jiook Hum Brain Mapp Research Articles Sex impacts the development of the brain and cognition differently across individuals. However, the literature on brain sex dimorphism in humans is mixed. We aim to investigate the biological underpinnings of the individual variability of sexual dimorphism in the brain and its impact on cognitive performance. To this end, we tested whether the individual difference in brain sex would be linked to that in cognitive performance that is influenced by genetic factors in prepubertal children (N = 9,658, ages 9–10 years old; the Adolescent Brain Cognitive Development study). To capture the interindividual variability of the brain, we estimated the probability of being male or female based on the brain morphometry and connectivity features using machine learning (herein called a brain sex score). The models accurately classified the biological sex with a test ROC–AUC of 93.32%. As a result, a greater brain sex score correlated significantly with greater intelligence (p (fdr) < .001, [Formula: see text]  = .011–.034; adjusted for covariates) and higher cognitive genome‐wide polygenic scores (GPSs) (p (fdr) < .001, [Formula: see text]  < .005). Structural equation models revealed that the GPS‐intelligence association was significantly modulated by the brain sex score, such that a brain with a higher maleness score (or a lower femaleness score) mediated a positive GPS effect on intelligence (indirect effects = .006–.009; p = .002–.022; sex‐stratified analysis). The finding of the sex modulatory effect on the gene–brain–cognition relationship presents a likely biological pathway to the individual and sex differences in the brain and cognitive performance in preadolescence. John Wiley & Sons, Inc. 2022-04-26 /pmc/articles/PMC9294341/ /pubmed/35471639 http://dx.doi.org/10.1002/hbm.25888 Text en © 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Kim, Kakyeong
Joo, Yoonjung Yoonie
Ahn, Gun
Wang, Hee‐Hwan
Moon, Seo‐Yoon
Kim, Hyeonjin
Ahn, Woo‐Young
Cha, Jiook
The sexual brain, genes, and cognition: A machine‐predicted brain sex score explains individual differences in cognitive intelligence and genetic influence in young children
title The sexual brain, genes, and cognition: A machine‐predicted brain sex score explains individual differences in cognitive intelligence and genetic influence in young children
title_full The sexual brain, genes, and cognition: A machine‐predicted brain sex score explains individual differences in cognitive intelligence and genetic influence in young children
title_fullStr The sexual brain, genes, and cognition: A machine‐predicted brain sex score explains individual differences in cognitive intelligence and genetic influence in young children
title_full_unstemmed The sexual brain, genes, and cognition: A machine‐predicted brain sex score explains individual differences in cognitive intelligence and genetic influence in young children
title_short The sexual brain, genes, and cognition: A machine‐predicted brain sex score explains individual differences in cognitive intelligence and genetic influence in young children
title_sort sexual brain, genes, and cognition: a machine‐predicted brain sex score explains individual differences in cognitive intelligence and genetic influence in young children
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294341/
https://www.ncbi.nlm.nih.gov/pubmed/35471639
http://dx.doi.org/10.1002/hbm.25888
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