Collective effects of common single nucleotide polymorphisms and genetic risk prediction in type 1 diabetes

Abstract

Type 1 diabetes (T1D) is a common autoimmune disease and may be related to multiple genetic and environmental risk factors. Previous genetic studies have focused on looking for individual polymorphic risk variants. Here, we studied the overall levels of genetic diversity in T1D patients by making use of a previously published study including 1865 cases and 2828 reference samples with genotyping data for 500 K common single nucleotide polymorphisms (SNPs). We determined the minor allele (MA) status of each SNP in the reference samples and calculated the total number of MAs or minor allele contents (MAC) of each individual. We found the average MAC of cases to be greater than that of the reference samples. By focusing on MAs with strong linkage to cases, we further identified a set of 112 SNPs that could predict 19.19% of cases. These results suggest that overall genetic variation over a threshold level may be a risk factor in T1D and provide a new genetic method for predicting the disorder.

Enrichment in conservative amino acid changes among fixed and standing missense variations in slowly evolving proteins

“…By using the overlap ratio method, we have verified that the vast majority of proteins show maximum distances between any two deeply diverged taxa, and only a small proportion, the slowest evolving, are still at the linear phase of changes ( Huang, 2010 ; Luo & Huang, 2016 ; Yuan et al, 2017 ). Variations at most genomic sites within human populations are also at optimum equilibrium, as evidenced by the observation that a slight increase above the present genetic diversity level in normal subjects is associated with patient populations suffering from complex diseases ( Gui, Lei & Huang, 2017 ; He et al, 2017 ; Lei & Huang, 2017 ; Lei et al, 2018 ; Yuan et al, 2012 ; Yuan et al, 2014 ; Zhu et al, 2015 ), as well as the observation that the sharing of SNPs among different human groups is an evolutionary rate-dependent phenomenon, with more sharing in fast evolving sequences ( Yuan et al, 2017 ). It is important to note that a protein in a complex species plays more roles than its orthologous protein in a species of less organismal complexity, as explained by the maximum genetic diversity hypothesis ( Hu et al, 2013 ; Huang, 2009 ; Huang, 2016 ).…”

Inhibitory Receptors and Pathways of Lymphocytes: The Role of PD-1 in Treg Development and Their Involvement in Autoimmunity Onset and Cancer Progression

“…Type 1 diabetes represents a multifactorial autoimmune disorder characterized by the destruction of pancreatic β cells by autoreactive T lymphocytes ( 83 ). Both genetics ( 84 , 85 ) and environmental factors ( 86 ) are involved in T1D pathogenesis. The autoimmune response directed against pancreatic islet cells leads to a slow progressive and selective destruction of these cells (a condition identified as primary autoimmune insulitis) and, over the years, to a clinically manifested disease ( 87 ).…”

Peer Review #2 of "Enrichment in conservative amino acid changes among fixed and standing missense variations in slowly evolving proteins (v0.1)"

“…By using the overlap ratio method, we have verified that the vast majority of proteins show maximum distances between any two deeply diverged taxa, and only a small proportion, the slowest evolving, are still at the linear phase of changes (Huang 2010;Luo & Huang 2016;Yuan et al 2017). Variations at most genomic sites within human populations are also at optimum equilibrium, as evidenced by the observation that a slight increase above the present genetic diversity level in normal subjects is associated with patient populations suffering from complex diseases (Gui et al 2017;He et al 2017;Lei et al 2018;Yuan et al 2012;…”