Analysis of Y chromosome haplogroups in Parkinson’s disease

Grenn, Francis P.; Makarious, Mary B.; Bandrés‐Ciga, Sara; Iwaki, Hirotaka; Singleton, Andrew B.; Nalls, Mike A.; Blauwendraat, Cornelis

doi:10.1093/braincomms/fcac277

Cited by 6 publications

(4 citation statements)

References 55 publications

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“…Recent GWAS studies have explored the causation behind gender differences in European cohorts. However, they have been unable to find any conclusive argument from the analyses of the autosomal and sex chromosomes [ 88 – 90 ]. A comprehensive meta-analysis of several diverse cohorts also did not offer any leads on gender differences [ 91 ].…”

Section: Challenges Of Understanding Genome-wide Association At a Mol...mentioning

confidence: 99%

Common genetic risk for Parkinson's disease and dysfunction of the endo-lysosomal system

Bhore,

Bogacki,

O'Callaghan

et al. 2024

Phil. Trans. R. Soc. B

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Parkinson's disease is a progressive neurological disorder, characterized by prominent movement dysfunction. The past two decades have seen a rapid expansion of our understanding of the genetic basis of Parkinson's, initially through the identification of monogenic forms and, more recently, through genome-wide association studies identifying common risk variants. Intriguingly, a number of cellular pathways have emerged from these analysis as playing central roles in the aetiopathogenesis of Parkinson's. In this review, the impact of data deriving from genome-wide analyses for Parkinson's upon our functional understanding of the disease will be examined, with a particular focus on examples of endo-lysosomal and mitochondrial dysfunction. The challenges of moving from a genetic to a functional understanding of common risk variants for Parkinson's will be discussed, with a final consideration of the current state of the genetic architecture of the disorder. This article is part of a discussion meeting issue ‘Understanding the endo-lysosomal network in neurodegeneration’.

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Section: Challenges Of Understanding Genome-wide Association At a Mol...mentioning

confidence: 99%

Common genetic risk for Parkinson's disease and dysfunction of the endo-lysosomal system

Bhore,

Bogacki,

O'Callaghan

et al. 2024

Phil. Trans. R. Soc. B

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“…Recently, a large-scale association study was reported that examined the association between Y haplogroups and the risk of Parkinson's disease. Grenn et al identified haplogroups, variants, and gene expression patterns potentially associated with Parkinson's disease risk in males using multiple large cohorts [Grenn et al, 2022] (shown in Table 1). They analyzed blood-based RNA sequence data obtained from the Accelerating Medicines Partnership-a Parkinson's disease initiative including 1,020 samples and RNA sequence data obtained from the North American Brain Expression Consortium including 171 samples to identify Y chromosome genes differentially expressed in cases and controls with specific haplogroups and specific tissues.…”

Section: Neuropsychiatric Disordersmentioning

confidence: 99%

Y Chromosome Genomic Variations and Biological Significance in Human Diseases and Health

Kuroki,

Fukami

2023

Cytogenet Genome Res

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The Y chromosome is a haploid genome unique to males with no genes essential for life. It is easily transmitted to the next generation without being repaired by recombination, even if a major genomic structural alteration occurs. On the other hand, the Y chromosome genome is basically a genomic region transmitted only from father to son, reflecting a male-specific inheritance between generations. The Y chromosome exhibits genomic structural differences among different ethnic groups and individuals. The Y chromosome was previously thought to affect only male-specific phenotypes, but recent studies have revealed associations between the Y chromosomes and phenotypes common to both males and females, such as certain types of cancer and neuropsychiatric disorders. This evidence was discovered with the finding of the mosaic loss of the Y chromosome in somatic cells. This phenomenon is also affected by environmental factors, such as smoking and aging. In the past, functional analysis of the Y chromosome has been elucidated by assessing the function of Y chromosome-specific genes and the association between Y chromosome haplogroups and human phenotypes. These studies are currently being conducted intensively. Additionally, the recent advance of large-scale genome cohort studies has increased the amount of Y chromosome genomic information available for analysis, making it possible to conduct more precise studies of the relationship between genome structures and phenotypes. In this review, we will introduce recent analyses using large-scale genome cohort data and previously reported association studies between Y chromosome haplogroups and human phenotypes, such as male infertility, cancer, cardiovascular system traits, and neuropsychiatric disorders. The function and biological role of the Y chromosome in human phenotypes will also be discussed.

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“…One study of Parkinson’s disease explored the association with Y chromosome haplogroups and single Y chromosome variants, albeit they did not find significant associations, which the authors note could be in part due to a large portion of the chromosome (30 Mb) being difficult to assess given its heterochromatic nature and the presence of repeats. 76 Similarly, no significant associations with multiple sclerosis have yet been identified with more recent Y chromosome data. 59…”

Section: Introductionmentioning

confidence: 95%

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

Neale,

Lona-Durazo,

Ryten

et al. 2024

Brain Communications

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

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Analysis of Y chromosome haplogroups in Parkinson’s disease

Cited by 6 publications

References 55 publications

Common genetic risk for Parkinson's disease and dysfunction of the endo-lysosomal system

Common genetic risk for Parkinson's disease and dysfunction of the endo-lysosomal system

Y Chromosome Genomic Variations and Biological Significance in Human Diseases and Health

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

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