Steroid hormone pathways, vitamin D and autism: a systematic review

Amestoy, Anouck; Baudrillard, Claire; Briot, Kellen; Pizano, Adrien; Bouvard, Manuel; Lai, Meng‐Chuan

doi:10.1007/s00702-022-02582-6

Cited by 6 publications

(3 citation statements)

References 93 publications

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“…Interestingly, the novel loci shared between SCZ and vitD levels were found in the proximity of genes ( DGKG , EMC2 ) which are connected to pathogenic neurodevelopmental processes, and to autism spectrum disorders. 99 , 100 Moreover, our results suggest that vitD may influence the resilience of the developing brain to adverse factors. This is a potential direction for future animal studies and research in large birth cohorts.…”

Section: Discussionmentioning

confidence: 61%

Genome-wide Association Analysis of Schizophrenia and Vitamin D Levels Shows Shared Genetic Architecture and Identifies Novel Risk Loci

Jahołkowski

Hindley

Shadrin

et al. 2023

Schizophrenia Bulletin

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Low vitamin D (vitD) levels have been consistently reported in schizophrenia (SCZ) suggesting a role in the etiopathology. However, little is known about the role of underlying shared genetic mechanisms. We applied a conditional/conjunctional false discovery rate approach (FDR) on large, nonoverlapping genome-wide association studies for SCZ (N cases = 53 386, N controls = 77 258) and vitD serum concentration (N = 417 580) to evaluate shared common genetic variants. The identified genomic loci were characterized using functional analyses and biological repositories. We observed cross-trait SNP enrichment in SCZ conditioned on vitD and vice versa, demonstrating shared genetic architecture. Applying the conjunctional FDR approach, we identified 72 loci jointly associated with SCZ and vitD at conjunctional FDR < 0.05. Among the 72 shared loci, 40 loci have not previously been reported for vitD, and 9 were novel for SCZ. Further, 64% had discordant effects on SCZ-risk and vitD levels. A mixture of shared variants with concordant and discordant effects with a predominance of discordant effects was in line with weak negative genetic correlation (rg = −0.085). Our results displayed shared genetic architecture between SCZ and vitD with mixed effect directions, suggesting overlapping biological pathways. Shared genetic variants with complex overlapping mechanisms may contribute to the coexistence of SCZ and vitD deficiency and influence the clinical picture.

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Section: Discussionmentioning

confidence: 61%

Genome-wide Association Analysis of Schizophrenia and Vitamin D Levels Shows Shared Genetic Architecture and Identifies Novel Risk Loci

Jahołkowski

Hindley

Shadrin

et al. 2023

Schizophrenia Bulletin

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“…Autism was previously associated with a decreased level of maternal serum sex hormone binding globulin 87 . This finding could imply an etiological association between sex hormone pathways and ASD status particularly in males 16,23 . Still in the Male-XWAS, we identified the gene PCDH19, also found in the Meta-XWAS.…”

Section: Discussionmentioning

confidence: 80%

“…21 . Sex hormones, known influencers of typical male and female brain development 22 , may also contribute to sex-varied penetrance in ASD 23 . For example, a surge of testosterone in the male fetus, combined with XY chromosomal determinants, may impact the neuroimmune system, affecting dendritic arborization 24 and the number of microglia and neurons 25 , hence contribute to the sexdifference biology of ASD.…”

Section: Introductionmentioning

confidence: 99%

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

Mendes,

Chen,

Engchuan

et al. 2024

Preprint

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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 in ASD pathogenesis, such asMECP2,DDX3X, andDMD. The "female protective effect" in ASD suggests that females may require a higher genetic burden to manifest similar symptoms as males, yet the mechanisms remain unclear. Despite technological advances in genomics, the complexity of the biological nature of sex chromosomes leave them underrepresented in genome-wide studies. Here, we conducted an X chromosome-wide association study (XWAS) using whole-genome sequencing data from 6,873 individuals with ASD (82% males) across Autism Speaks MSSNG, Simons Simplex Cohort SSC, and Simons Foundation Powering Autism Research SPARK, alongside 8,981 population controls (43% males). We analyzed 418,652 X-chromosome variants, identifying 59 associated with ASD (p-values 7.9×10⁻⁶ to 1.51×10⁻⁵), surpassing Bonferroni-corrected thresholds. Key findings include significant regions on chrXp22.2 (lead SNP=rs12687599, p=3.57×10⁻⁷) harboringASB9/ASB11, and another encompassingDDX53/PTCHD1-ASlong non-coding RNA (lead SNP=rs5926125, p=9.47×10⁻⁶). When mapping genes within 10kb of the 59 most significantly associated SNPs, 91 genes were found, 17 of which yielded association with ASD (GRPR,AP1S2,DDX53,HDAC8,PCDH19,PTCHD1,PCDH11X,PTCHD1-AS,DMD,SYAP1,CNKSR2,GLRA2,OFD1,CDKL5,GPRASP2,NXF5,SH3KBP1).FGF13emerged as a novel X-linked ASD candidate gene, highlighted by sex-specific differences in minor allele frequencies. These results reveal significant new insights into X chromosome biology in ASD, confirming and nominating genes and pathways for further investigation.

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