Classification of common human diseases derived from shared genetic and environmental determinants

Abstract

In this study, we used insurance claims for over a third of the entire United States population to create a subset of 128,989 families (481,657 unique individuals). We then used these data to: 1) estimate the heritability and familial environmental patterns of 149 diseases, and; 2) infer the genetic and environmental correlations between disease pairs from a set of 29 complex diseases. The majority (52 out of 65) of our study’s heritability estimates matched earlier reports, and 84 of our estimates appear to be obtained for the first time. We used correlation matrices to compute environmental and genetic disease classifications and corresponding reliability measures. Among unexpected observations, we found that migraine, typically classified as a disease of the central nervous system, appeared to be most genetically similar to irritable bowel syndrome and most environmentally similar to cystitis and urethritis, all of which are inflammatory diseases.

Bias in Mendelian randomization due to assortative mating

“…This study evidenced that bias due to assortative mating is of greater concern when the strength of assortment is strong, when the outcome phenotype is highly heritable, and when the process has been going on over many generations. Many human phenotypes are suggested to have high heritability in the populations where they were studied (Speed, Cai, Johnson, Nejentsev, & Balding, ; Wang, Gaitsch, Poon, Cox, & Rzhetsky, ). In our simulations, cross‐trait assortative on X and Y mating resulted in realistic between‐parents correlations (Supporting Information Table ).…”

Future Preventive Gene Therapy of Polygenic Diseases from a Population Genetics Perspective

“…This research followed suit: SNP effects were treated in terms of relative risk, and PRSs were expressed in terms of the sum of the logarithm of RR. This method is also justified by the fact that the majority of EMODs have a prevalence of less than 2%, as exemplified by RA [58], LE [59], schizophrenia and bipolar disorder [60,96,97], and Crohn's disease [61,62], with only a small number of diseases such as asthma [53] approaching a prevalence of 10% [65]. Dupuytren's disease, which has a prevalence of more than 30% in some Northern European ethnicities, although it is lower in most of the world by 1-3 levels of magnitude, is an interesting example that was examined in this research.…”

“…The first set of simulations evaluated the blending admixture of two simulated populations with equal liability to a disease. The disease heritability was set at 50%, the mid-range heritability of polygenic diseases [65,66]. The disease SNP sets were built using the common low-effect genetic architecture, and the population genetics simulation progressed through generations.…”

“…The heritability of EMODs usually ranges from 30% to 80%, as documented by Wang et al [65] and Polubriaginof et al [66]. A heritability level of 50% was chosen for most simulations and analyses to represent a typical EMOD, and the common low-effect-size genetic architecture SNP set was assembled accordingly, as noted in section 4.3.…”

Molecular Inverse Comorbidity between Alzheimer’s disease and Lung Cancer: new insights from Matrix Factorization

“…Indeed, several computational studies have inferred DD relationships, starting from the "Human Disease Network" where diseases were connected when sharing disease genes [13], to the "multiplex network of human diseases" composed by genotypeand phenotype-based layers that propose new disease-associations [14]. More importantly, DD relationships have also been systematically identified by epidemiological studies, working at the level of populations and looking for the co-occurrence of different diseases in the same patients by using medical claims [15], medical records [16] and insurance claims [17]. The higher than expected risk of developing pancreatic cancer in patients suffering for type II diabetes [18] and of developing lung cancer in asthma patients [19] are among the most renown examples of cancer-related comorbidities.…”