Same genes, different brains: why women show more genetic links to brain size
A major genetic study of over 31,000 people found that while men and women's brains are shaped by largely the same genes, researchers identified more genes linked to brain volume in women than in men. The finding could help explain why neurological and mental health disorders affect the sexes differently—and suggests future drug development and diagnostics may need sex-specific approaches.
Originaltitel: Sex-stratified insights into the genetics of brain volumes in late adulthood.
Könsskillnader i hjärnvolym påverkas av gemensamma genetiska mekanismer, inte nämnvärt olika mellan män och kvinnor i sen vuxenålder. Denna slutsats bygger på en genomsökning av 31 480 personer från UK Biobank, där forskare identifierade vilka genvarianter som påverkar 257 hjärnregioner separat för varje kön. Analysen avslöjade att heritabilitet och genetiska korrelationer mellan könen var likartade. Många genetiska loci återfanns i båda könen, men kvinnor hade fler identifierade gener kopplade till hjärnvolym än män — särskilt i limbiska regioner som insula, cingulat cortex, hippocampus och amygdala. Resultaten från Universitetet i Oslo och kanadensiska institutioner relevanta för utveckling av könsstratifierad psykiatrisk medicinering och diagnostik. För bolagsbyggare inom neuropsykiatrisk farmakologi underlättar dessa fynd målval för prekliniska program där könsgenetisk variation kan påverka effektivitet och säkerhet.
BACKGROUND: The prevalence, timing and disease course of mental and neurological disorders vary according to sex, yet the neurogenetic mechanisms underlying sex differences in brain disorders remain poorly understood. While sex chromosomes and hormones contribute to sex differences in brain biology, previous studies suggest a role for autosomal genetic variation as well. METHODS: We investigated autosomal genetic associations with brain volumes in 15,740 females and 15,740 males from the UK Biobank, matched for age and scan site, using sex-stratified genome-wide association analyses. We applied a multivariate genome-wide approach (MOSTest) across 257 brain regions and complemented these analyses with region-specific univariate genome-wide association studies. RESULTS: Heritability estimates and genetic correlations were highly similar between females and males in late adulthood, indicating largely shared genetic influences on brain volumes. Many loci reaching genome-wide significance in one sex also showed signal in the other. Gene mapping in these loci yielded a greater total number of brain-volumes associated genes in females than in males. Variability in the number of mapped genes was particularly pronounced in limbic regions such as the insula, cingulate cortex, hippocampus and amygdala. CONCLUSION: Overall, our findings contribute to a better understanding of autosomal genetic influences on brain volumes in males and females and may inform future studies examining sex variability in neurobiological mechanisms relevant to brain disorders.