Better together against genetic effect heterogeneity:
a sex-combined interaction analysis of testosterone
levels in the UK Biobank data

Lin, Boxi; Sun, Lei

doi:10.21203/rs.3.rs-2143600/v1

Cited by 1 publication

(1 citation statement)

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“…Traditional XWAS which tests for the primary additive effect, can overlook these variants as effects with varying directions might negate each other in a linear model, leading to the “masking of genetic effect” 108 . Through meta-analysis using Stouffer’s method 111 , we identified variants overlooked in the sex-agnostic XWAS 112 ( Fig. S15 ).…”

Section: Resultsmentioning

confidence: 99%

The pivotal role of the X-chromosome in the genetic architecture of the human brain

Jiang,

Sullivan,

et al. 2023

Preprint

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Genes on the X-chromosome are extensively expressed in the human brain, resulting in substantial influences on brain development, intellectual disability, and other brain-related disorders. To comprehensively investigate the X-chromosome's impact on the cerebral cortex, white matter tract microstructures, and intrinsic and extrinsic brain functions, we examined 2,822 complex brain imaging traits obtained from n = 34,000 subjects in the UK Biobank. We unveiled potential autosome-X-chromosome interaction, while proposing an atlas of dosage compensation (DC) for each set of traits. We observed a pronounced X-chromosome impact on the corticospinal tract and the functional amplitude and connectivity of visual networks. In association studies, we identified 50 genome-wide significant trait-locus pairs enriched in Xq28, 22 of which replicated in independent datasets (n = 4,900). Notably, 13 newly identified pairs were in the X-chromosome's non-pseudo-autosomal regions (NPR). The volume of the right ventral diencephalon shared genetic architecture with schizophrenia and educational attainment in a locus indexed by rs2361468 (located ~3kb upstream of PJA1, a conserved and ubiquitously expressed gene implicated in multiple psychiatric disorders). No significant associations were identified in the pseudo-autosomal regions (PAR) or the Y-chromosome. Finally, we explored sex-specific associations on the X-chromosome and compared differing genetic effects between sexes. We found much more associations can be identified in males (33 versus 9) given a similar sample size. In conclusion, our research provides invaluable insights into the X-chromosome's role in the human brain, contributing to the observed sex differences in brain structure and function.

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Section: Resultsmentioning

confidence: 99%