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

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Сен. 1, 2023

Abstract Genes on the X-chromosome are extensively expressed in human brain. However, little is known for X-chromosome’s impact brain anatomy, microstructure, and functional network. We examined 1,045 complex imaging traits from 38,529 participants UK Biobank. unveiled potential autosome-X-chromosome interactions, while proposing an atlas outlining dosage compensation (DC) traits. Through extensive association studies, we identified 72 genome-wide significant trait-locus pairs (including 29 new associations) that share genetic architectures with brain-related disorders, notably schizophrenia. Furthermore, discovered unique sex-specific associations assessed variations effects between sexes. Our research offers critical insights into role brain, underscoring its contribution to differences observed structure functionality One-sentence Summary investigated of sex

Язык: Английский

---

Comprehensive whole-genome analyses of the UK Biobank reveal significant sex differences in both genotype missingness and allele frequency on the X chromosome

Human Molecular Genetics, Год журнала: 2023, Номер 33(6), С. 543 - 551

Опубликована: Дек. 9, 2023

Abstract The UK Biobank is the most used dataset for genome-wide association studies (GWAS). GWAS of sex, essentially sex differences in minor allele frequencies (sdMAF), has identified autosomal SNPs with significant sdMAF, including Biobank, but X chromosome was excluded. Our recent report multiple regions on using short-read sequencing other datasets. We performed a whole genome sdMAF analysis, ~410 k white British individuals from array genotyped, imputed or exome data. observed marked chromosome, particularly at boundaries between pseudo-autosomal (PAR) and non-PAR (NPR), as well throughout NPR, consistent our earlier report. A small fraction also showed sdMAF. Using centrally data, which relied mostly low-coverage sequence, resulted 2.1% NPR displays some heterozygous genotype calls males. Genotyping, imputation chromosomal requires further attention to ensure integrity downstream analysis.

Язык: Английский

---

Genetic correlations of alcohol consumption and alcohol use disorder with sex hormone levels in females and males

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Фев. 28, 2024

Background Alcohol consumption behaviors and alcohol use disorder risk presentation differ by sex, these complex traits are associated with blood concentrations of the steroid sex hormones, testosterone estradiol, their regulatory binding proteins, hormone globulin (SHBG) albumin. Genetic variation is disorder, as well levels hormones proteins. Methods To assess contribution genetic factors to previously described phenotypic associations between alcohol-use sex-hormone levels, we estimated correlations (r_g) using summary statistics from prior published, large sample size genome-wide association studies (GWAS) consumption, dependence, testosterone, SHBG, Results For observed positive correlation (i.e. effects in same direction) total males (r_g = 0.084, p 0.007) trends toward bioavailable 0.060, 0.084) SHBG 0.056, 0.086) albumin a sex-combined cohort 0.082, 0.015); however females, 0.089, 0.004) trend negative opposite directions) -0.064, 0.032). females -0.106, 0.024) BMI-adjusted 0.119, 0.017). Several differed were not direction corresponding associations. Conclusions Findings suggest that shared may contribute both sexes, dependence males. However, relative contributions heritable environmental contributing more females.

Язык: Английский

---

Leveraging sex-genetic interactions to understand brain disorders: recent advances and current gaps

Brain Communications, Год журнала: 2024, Номер 6(3)

Опубликована: Янв. 1, 2024

Abstract It is established that there are sex differences in terms of prevalence, age onset, clinical manifestations, and response to treatment for a variety brain disorders, including neurodevelopmental, psychiatric, neurodegenerative disorders. Cohorts increasing sample sizes with diverse data types collected, genetic, transcriptomic and/or phenotypic data, providing the building blocks permit analytical designs test sex-biased genetic variant-trait associations, transcriptional regulation. Such molecular assessments can contribute our understanding manifested between sexes offering future possibility delivering personalized therapy females males. With intention raising profile this field as research priority, review aims shed light on importance investigating sex-genetic interactions focusing two areas: (i) associations (ii) transcriptomics (i.e. gene expression, transcript usage regulation). We specifically discuss recent advances field, current gaps provide considerations studies.

Язык: Английский

---

Chromosome X-Wide Common Variant Association Study (XWAS) in Autism Spectrum Disorder

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 18, 2024

Autism Spectrum Disorder (ASD) displays a notable male bias in prevalence. Research into rare (<0.1) genetic variants on the X chromosome has implicated over 20 genes ASD pathogenesis, such as

Язык: Английский

---