Minor alleles of common SNPs quantitatively affect traits/diseases and are under both positive and negative selection

A new understanding of the genetic equidistance result of Margoliash that originally inspired the neutral theory has disproven the theory’s implicit message of a forever correlation between genetic distance and time. The more complete Maximum Genetic Diversity (MGD) hypothesis is a newly proposed alternative and considers genetic diversity today to be mostly at an optimum equilibrium. To use the MGD to help solve major biomedical problems, we here asked whether extreme values in genetic diversity as represented by the amount of minor alleles (MAs) of common SNPs may represent extreme trait values and common diseases. We analyzed panels of genetic reference populations and identified the MAs in each panel and the MA fractions that each strain carried. We also analyzed 21 published GWAS datasets of human diseases and identified the MA fractions of each case or control. MA amounts in model organisms were nearly linearly linked to quantitative variations in numerous traits including life span, tumor susceptibility, anxiety, depression, learning and memory, sensitivity to alcohol, methamphetamine, cocaine, pain and anti-psychotic drugs, levels in glucose, insulin, resistin, IL17, iron, and dopamine, and two correlated traits poor reproductive fitness and strong immunity. Similarly, in Europeans or European Americans, enrichment of MAs of fast but not slow evolutionary rate was linked to autoimmune and numerous other diseases including type 2 diabetes, Parkinson’s disease, psychiatric disorders, alcohol and cocaine addictions, cancer, and less life span. Therefore, both high and low MA amounts correlated with extreme values in many traits and are hence negatively selected, indicating that most MAs may be nearly neutral or slightly deleterious due to both positive and negative selection. These results add further evidence for the MGD hypothesis and open a new avenue of inquiry into the genetic basis of complex traits/diseases.