Identification of Potential Pleiotropic Genes for Immune and Skeletal Diseases Using Multivariate MetaCCA Analysis

He, Pei; Cao, Rong; Dèng, Fēi; Lei, Shu Feng

doi:10.2174/1389202923666211223115214

Cited by 3 publications

(2 citation statements)

References 29 publications

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“…Nevertheless, it is highly expressed in immune system cells ( 40 ) and genetically associated with several immune-related diseases, hepatitis, and dermatologic disorders, according to the GWAS catalog ( 30 ). Interestingly, TSBP1-AS1 is located in the major histocompatibility complex (MHC) region ( 41 ). Previous studies have reported that the clinical features of migraine may be influenced by SNPs located in the MHC region ( 42 , 43 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of genetic risk loci for depression and migraine comorbidity in Han Chinese residing in Taiwan

Tsai

Tsai²,

Liang³

et al. 2023

Front. Psychiatry

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IntroductionThe genetic association between depression and migraine has not been well investigated in Asian populations. Furthermore, the genetic basis of depression and comorbid migraine subtypes remains nebulous. Hence, in the current study we investigate the susceptibility loci associated with depression and migraine comorbidity in the Han Chinese population in Taiwan.MethodsWe perform a genome-wide association study involving 966 migraine patients, with or without comorbid depression. Genotyping is performed using participant genomic DNA. Association analyses are performed for the entire migraine cohort (subgroups: episodic migraine, chronic migraine, and migraine with or without aura).ResultsResults show that the single nucleotide polymorphism variants of the CDH4 intron region (rs78063755), NTRK3-AS1 downstream region (rs57729223), and between LINC01918 and GPR45 (rs2679891) are suggestively associated with depression. Twenty additional susceptibility loci occur within the subgroups. A multivariate association study demonstrated that a variant in the intron region of CDH4 rs78063755 was associated with Beck Depression Inventory and Migraine Disability Assessment scores.DiscussionThe findings of this study identify several genetic loci suggestively associated with depression among migraine patients in the Han Chinese population. Moreover, a potential genetic basis has been characterized for depression and migraine comorbidity, thus providing genetic candidates for further investigation.

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Section: Discussionmentioning

confidence: 99%

Identification of genetic risk loci for depression and migraine comorbidity in Han Chinese residing in Taiwan

Tsai

Tsai²,

Liang³

et al. 2023

Front. Psychiatry

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show abstract

“…The gene is also upregulated in the synovial biopsies in the cases 54 . Beyond the gene body, we found a genetic variant in the MICD pseudogene, which was reported to be a potential pleiotropic gene for immune and skeletal disease, including psoriasis 55 (Supplementary Data 3).…”

Section: Genoboost Scores Allow Inference Of the Mode Of Inheritancementioning

confidence: 99%

A polygenic score method boosted by non-additive models

Ohta,

Tanigawa,

Suzuki

et al. 2024

Nat Commun

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Dominance heritability in complex traits has received increasing recognition. However, most polygenic score (PGS) approaches do not incorporate non-additive effects. Here, we present GenoBoost, a flexible PGS modeling framework capable of considering both additive and non-additive effects, specifically focusing on genetic dominance. Building on statistical boosting theory, we derive provably optimal GenoBoost scores and provide its efficient implementation for analyzing large-scale cohorts. We benchmark it against seven commonly used PGS methods and demonstrate its competitive predictive performance. GenoBoost is ranked the best for four traits and second-best for three traits among twelve tested disease outcomes in UK Biobank. We reveal that GenoBoost improves prediction for autoimmune diseases by incorporating non-additive effects localized in the MHC locus and, more broadly, works best in less polygenic traits. We further demonstrate that GenoBoost can infer the mode of genetic inheritance without requiring prior knowledge. For example, GenoBoost finds non-zero genetic dominance effects for 602 of 900 selected genetic variants, resulting in 2.5% improvements in predicting psoriasis cases. Lastly, we show that GenoBoost can prioritize genetic loci with genetic dominance not previously reported in the GWAS catalog. Our results highlight the increased accuracy and biological insights from incorporating non-additive effects in PGS models.

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Genome‑wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan

Yang,

Liu,

et al. 2024

Mol Med Rep

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Psoriasis is a chronic inflammatory dermatological disease, and there is a lack of understanding of the genetic factors involved in psoriasis in Taiwan. To establish associations between genetic variations and psoriasis, a genome-wide association study was performed in a cohort of 2,248 individuals with psoriasis and 67,440 individuals without psoriasis. Using the ingenuity pathway analysis software, biological networks were constructed. Human leukocyte antigen (HLA) diplotypes and haplotypes were analyzed using Attribute Bagging (HIBAG)-R software and chi-square analysis. The present study aimed to assess the potential risks associated with psoriasis using a polygenic risk score (PRS) analysis. The genetic association between single nucleotide polymorphisms (SNPs) in psoriasis and various human diseases was assessed by phenome-wide association study. METAL software was used to analyze datasets from China Medical University Hospital (CMUH) and BioBank Japan (BBJ). The results of the present study revealed 8,585 SNPs with a significance threshold of P<5×10 −8 , located within 153 genes strongly associated with the psoriasis phenotype, particularly on chromosomes 5 and 6. This specific genomic region has been identified by analyzing the biological networks associated with numerous pathways, including immune responses and inflammatory signaling. HLA genotype analysis indicated a strong association between HLA-A*02:07 and HLA-C*06:02 in a Taiwanese population. Based on our PRS analysis, the risk of psoriasis associated with the SNPs identified in the present study was quantified. These SNPs are associated with various dermatological, circulatory, endocrine, metabolic, musculoskeletal, hematopoietic and infectious diseases. The meta-analysis results indicated successful replication of a study conducted on psoriasis in the BBJ. Several genetic loci are significantly associated with susceptibility to psoriasis in Taiwanese individuals. The present study contributes to our understanding of the genetic determinants that play a role in susceptibility to psoriasis. Furthermore, it provides valuable insights into the underlying etiology of psoriasis in the Taiwanese community.

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Identification of Potential Pleiotropic Genes for Immune and Skeletal Diseases Using Multivariate MetaCCA Analysis

Cited by 3 publications

References 29 publications

Identification of genetic risk loci for depression and migraine comorbidity in Han Chinese residing in Taiwan

Identification of genetic risk loci for depression and migraine comorbidity in Han Chinese residing in Taiwan

A polygenic score method boosted by non-additive models

Genome‑wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan

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