Ohn Jung Hun
Division of General Internal Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
J Am Med Inform Assoc. 2017 Sep 1;24(5):921-926. doi: 10.1093/jamia/ocx026.
The aim of the study was to comprehensively explore the genetic susceptibility correlations among diseases and traits from large-scale individual genotype data.
Based on a knowledge base of genetic variants significantly (P < 5 × 10 -8 ) linked with human phenotypes, genetic risk scores (GRSs) of diseases or traits were calculated for 2504 individuals with whole-genome sequencing data from the 1000 Genomes Project. Associations between diseases/traits were statistically evaluated by pairwise correlation analysis of GRSs. Overlaps between the genetic susceptibility correlations and disease comorbidity associations from hospital claims data in more than 30 million patients in United States were assessed.
Correlation analysis of GRSs revealed 823 significant correlations among 78 diseases and 89 traits (false discovery rate adjusted P -value or Q -value < 0.01). It is noticeable that GRSs were correlated in 464 associations (56.4%) even if they were combinations of distinct sets of risk variants without chromosomal linkage, suggesting the presence of genetic interactions beyond chromosome position. When 312 significant genetic susceptibility correlations between diseases were compared to nationwide disease comorbidity correlations obtained from data from 32 million Medicare claims in the United States, 108 overlaps (34.6%) were found that had both genetic susceptibility and epidemiologic comorbid correlations.
The study suggests that common genetic background exists between diseases and traits with epidemiologic associations. The GRS correlation approach provides a rich source of candidate associations among diseases and traits from the genetic perspective, warranting further epidemiologic studies.
本研究旨在从大规模个体基因型数据中全面探索疾病与性状之间的遗传易感性关联。
基于与人类表型显著相关（P < 5×10 -8）的遗传变异知识库，为来自千人基因组计划的2504名有全基因组测序数据的个体计算疾病或性状的遗传风险评分（GRS）。通过GRS的成对相关性分析对疾病/性状之间的关联进行统计学评估。评估了美国超过3000万患者医院索赔数据中的遗传易感性关联与疾病共病关联之间的重叠情况。
GRS的相关性分析揭示了78种疾病和89个性状之间存在823个显著相关性（错误发现率调整后的P值或Q值<0.01）。值得注意的是，即使GRS是无染色体连锁的不同风险变异集的组合，它们在464个关联（56.4%）中仍存在相关性，这表明存在超越染色体位置的基因相互作用。当将疾病之间的312个显著遗传易感性关联与从美国3200万医疗保险索赔数据中获得的全国性疾病共病相关性进行比较时，发现有108个重叠（34.6%）同时具有遗传易感性和流行病学共病相关性。
该研究表明，具有流行病学关联的疾病和性状之间存在共同的遗传背景。GRS相关性方法从遗传角度为疾病和性状之间的候选关联提供了丰富来源，值得进一步进行流行病学研究。
