Garvan Institute of Medical Research, Sydney, NSW, Australia.
Children's Cancer Institute, University of New South Wales, Sydney, NSW, Australia.
Nat Commun. 2020 Jan 23;11(1):435. doi: 10.1038/s41467-019-14079-0.
Population health research is increasingly focused on the genetic determinants of healthy ageing, but there is no public resource of whole genome sequences and phenotype data from healthy elderly individuals. Here we describe the first release of the Medical Genome Reference Bank (MGRB), comprising whole genome sequence and phenotype of 2570 elderly Australians depleted for cancer, cardiovascular disease, and dementia. We analyse the MGRB for single-nucleotide, indel and structural variation in the nuclear and mitochondrial genomes. MGRB individuals have fewer disease-associated common and rare germline variants, relative to both cancer cases and the gnomAD and UK Biobank cohorts, consistent with risk depletion. Age-related somatic changes are correlated with grip strength in men, suggesting blood-derived whole genomes may also provide a biologic measure of age-related functional deterioration. The MGRB provides a broadly applicable reference cohort for clinical genetics and genomic association studies, and for understanding the genetics of healthy ageing.
人口健康研究越来越关注健康老龄化的遗传决定因素，但目前还没有公开的来自健康老年人的全基因组序列和表型数据资源。在这里，我们描述了 Medical Genome Reference Bank（MGRB）的首次发布，它包含了 2570 名澳大利亚老年人的全基因组序列和表型数据，这些老年人经过了癌症、心血管疾病和痴呆症的筛查。我们分析了 MGRB 中的核基因组和线粒体基因组中的单核苷酸、插入缺失和结构变异。与癌症病例以及 gnomAD 和 UK Biobank 队列相比，MGRB 个体的与疾病相关的常见和罕见种系变异更少，这与风险降低一致。与年龄相关的体细胞变化与男性的握力相关，这表明血液衍生的全基因组也可能提供与年龄相关的功能恶化的生物学测量。MGRB 为临床遗传学和基因组关联研究以及理解健康老龄化的遗传学提供了一个广泛适用的参考队列。
