X and Y gene dosage effects are primary contributors to human sexual dimorphism: The case of height

• 成果类型: Article
• 署名作者: Berry, Alexander S. F.; Finucane, Brenda M.; Myers, Scott M.; Martin, Christa L.; Ledbetter, David H.; Willard, Huntington F.; Oetjens, Matthew T.
• 署名单位: Geisinger Health System; State University System of Florida; Florida State University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13815
• DOI: 10.1073/pnas.2503039122
• 发表日期: 2025-06-03
• 关键词: short stature; turner-syndrome; chromosome aneuploidies; dna methylation; growth failure; adult height; shox; klinefelter; expression; inactivation

摘要

Many human phenotypic traits vary between the sexes, including adult height for which males are, on average, 13 cm taller than females. The biological mechanisms for this sexual dimorphism are not entirely understood. One hypothesis to explain the sexual dimorphism in height relates to differential expression in males and females of SHOX, a height-related expression is reduced on the inactive X chromosome (Xi), compared to the active X in females. Sex chromosome aneuploidies (SCAs), characterized by an atypical number of X and/or Y chromosomes, serve as informative models for investigating PAR1-related gene dosage effects. Here, we leveraged three large biobanks to study 928,605 individuals, including 1,225 adults with SCAs: 45,X (n = 95), 47,XXY (n = 505), 47,XYY (n = 290), and 47,XXX (n = 335). By modeling height across individuals with various sex chromosome complements, we quantified the contributions of five sex-related genomic contributors to height, chromosome explained 22.6% of the observed difference in height between 46,XY males and in females results in a net difference in height between the sexes.