在祖先多样化的队列中,罕见变异分析揭示了新的ADHD风险基因
Seulgi Jung1,2, Madison Caballero1,2, Emily Olfson3,4
1Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
medRxiv : the preprint server for health sciences
|January 27, 2025
概括
研究人员通过分析罕见的遗传变体,确定了15种高自信度ADHD风险基因. 这项研究增强了对注意力缺陷/多动症障碍的理解.
科学领域:
- 遗传学 是一个遗传学.
- 神经发育障碍 神经发育障碍
- 分子生物学分子生物学
背景情况:
- 注意缺陷/多动障碍 (ADHD) 是一种高度遗传的神经发育障碍.
- 目前尚不完全了解ADHD的遗传结构,特别是罕见编码变异的作用.
- 罕见的变异可以显著影响基因功能,并导致疾病风险.
研究的目的:
- 研究罕见编码变异在ADHD遗传结构中的作用.
- 识别新的ADHD风险基因和相关的生物通路.
- 探索导致ADHD病变的分子机制.
主要方法:
- 对来自不同祖先队伍的大规模DNA测序数据集的分析.
- 在受约束的基因中识别和丰富分析罕见的蛋白质截断和有害的误解变异.
- 与全基因组关联研究 (GWAS) 数据和蛋白质-蛋白质相互作用网络的集成.
- 单细胞转录形状分析以检查基因表达模式.
主要成果:
- 进化受约束基因中罕见变异的显著丰富,确定了15个高度自信的ADHD风险基因,包括KDM5B.
- 在突触组织,神经元发育和染色体调节中涉及的9个丰富的生物通路.
- 染色体调节器被确定为蛋白质与蛋白质相互作用网络中的中心枢纽.
- 证实神经元和质细胞中的基因表达,在寡头细胞亚型中具有特定的模式.
结论:
- 这项研究通过突出罕见编码变异的作用,显著提高了对ADHD遗传结构的理解.
- 已识别的风险基因和途径为ADHD的核心分子机制提供了洞察力.
- 这些发现为未来治疗注意力缺陷/多动症障碍的治疗开发提供了有希望的途径.
相关概念视频
Attention-Deficit/Hyperactivity Disorder
36
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by persistent inattention, hyperactivity, and impulsivity. It affects approximately 5-8% of children globally, with around 60-70% of cases persisting into adulthood. ADHD has significant implications for educational attainment, social interactions, and occupational success.
Diagnostic Criteria and Symptoms
To diagnose ADHD, symptoms must manifest before age 12 and be evident across multiple settings....
Diagnostic Criteria and Symptoms
To diagnose ADHD, symptoms must manifest before age 12 and be evident across multiple settings....
36
Human Genetics
528
Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
The complex relationship between genetics and psychology is observable through common biological components such...
528
Pleiotropy
39.6K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
39.6K
Behavioral Genetics and Its Designs
322
Behavior genetics explores how genetic inheritance influences human behavior. It focuses on how genes, passed from parents to offspring, contribute to the development of behavioral traits and tendencies. This branch of genetics seeks to understand the complex interplay between inherited genetic factors and environmental influences in shaping our behaviors.
The primary methodologies used in behavior genetics include family studies, twin studies, and adoption studies, each providing unique...
The primary methodologies used in behavior genetics include family studies, twin studies, and adoption studies, each providing unique...
322
Genome-wide Association Studies-GWAS
12.4K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
12.4K
Incomplete Dominance
21.0K
Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.
21.0K


