Regional autozygosity association with albumin-to-creatinine ratio reveals a novel FTO region in an Indigenous Australian population.

IF 3.7 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Vignesh Arunachalam, Kim N Tran, Wendy Hoy, Rodney A Lea, Shivashankar H Nagaraj
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Abstract

The genetic distinctiveness of Indigenous Australian populations is well established, yet the Tiwi population remains underrepresented in genetic research. Due to their prolonged geographic isolation, these populations are prone to increased runs of homozygosity (ROH). We investigated the genetic diversity of the Tiwi population, isolated from mainland Australia for decades, based on ROH and their associations with clinical traits. We analyzed 455 whole genome sequences to identify population structure via PCA and performed a comparison with UK Biobank, Melanesian, and Polynesian cohorts. ROH assessment and genome-wide and regional measures of homozygosity were used to explore associations between clinical traits and autozygosity. Our analysis revealed distinct genetic characteristics of the Tiwi population that aligned closely with those of the Melanesian cohort. Tiwi individuals exhibited an increased burden of ROH, particularly in LINC0109, FMLN1, and RPL17P45 genes on chromosomes 2, 17, and 18, respectively, indicating prolonged isolation and genetic drift. A positive correlation was observed between genomic FROH and albumin-to-creatinine ratio (ACR) levels, suggesting a potential link between autozygosity and renal health markers. Furthermore, regional autozygosity association analysis revealed an association between elevated ACR and a region in FTO, implicating its role in obesity, kidney disease, and cardiovascular conditions. Importantly, we found that this association is strong under the recessive model. This research lays a robust foundation for further exploration of ROH mapping and its implications for disease susceptibility within Indigenous communities worldwide.

区域自合子与白蛋白与肌酐比值的关联揭示了澳大利亚土著人口中一个新的FTO区域。
澳大利亚土著人口的遗传独特性已经确立,但提维人在遗传研究中的代表性仍然不足。由于其长期的地理隔离,这些种群容易增加纯合性(ROH)。基于ROH及其与临床特征的关联,我们调查了从澳大利亚大陆分离了几十年的提维人群的遗传多样性。我们分析了455个全基因组序列,通过PCA确定种群结构,并与UK Biobank、美拉尼西亚和波利尼西亚队列进行了比较。使用ROH评估和全基因组和区域纯合子测量来探索临床特征与自合子之间的关系。我们的分析揭示了提维人群与美拉尼西亚人群密切相关的独特遗传特征。Tiwi个体表现出增加的ROH负担,特别是在染色体2、17和18上的LINC0109、FMLN1和RPL17P45基因,表明分离时间延长和遗传漂变。在基因组FROH和白蛋白与肌酐比值(ACR)水平之间观察到正相关,表明自合子和肾脏健康指标之间存在潜在联系。此外,区域自合子关联分析显示ACR升高与FTO的一个区域之间存在关联,暗示其在肥胖、肾脏疾病和心血管疾病中的作用。重要的是,我们发现这种关联在隐性模型下很强。本研究为进一步探索ROH制图及其对全球土著社区疾病易感性的影响奠定了坚实的基础。
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来源期刊
European Journal of Human Genetics
European Journal of Human Genetics 生物-生化与分子生物学
CiteScore
9.90
自引率
5.80%
发文量
216
审稿时长
2 months
期刊介绍: The European Journal of Human Genetics is the official journal of the European Society of Human Genetics, publishing high-quality, original research papers, short reports and reviews in the rapidly expanding field of human genetics and genomics. It covers molecular, clinical and cytogenetics, interfacing between advanced biomedical research and the clinician, and bridging the great diversity of facilities, resources and viewpoints in the genetics community. Key areas include: -Monogenic and multifactorial disorders -Development and malformation -Hereditary cancer -Medical Genomics -Gene mapping and functional studies -Genotype-phenotype correlations -Genetic variation and genome diversity -Statistical and computational genetics -Bioinformatics -Advances in diagnostics -Therapy and prevention -Animal models -Genetic services -Community genetics
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