How evolution of modern-day humans has influenced mental illness

As discussed often in these GEITP pages, psychiatric disorders represent multifactorial traits (i.e. phenotypes caused by the contribution of hundreds if not thousands of gene mutations, plus epigenetic effects, plus environmental adversities that can accumulate over decades of time). Other multifactorial traits include obesity, type-2 diabetes, various types of cancers, and drug efficacy as well as risk of toxicity. Hence, whenever possible, GEITP likes to examine the gene-environment interactions.

The [attached] Nov 2o17 editorial describes how “genetic predisposition (risk) of mental illness” might have evolved over hundreds of generations during the past 300K to 600K years. Just as with the previous note we sent earlier today (about influence of Neaderthal variants on modern humans), the attached editorial summarizes several other presentations at the Am. Soc. of Human Genetics annual meeting in late October. One project found that evolution selected for DNA variants that are thought to be protective against schizophrenia [see attached earlier report from Nov 2o16]. Authors used the singleton density score (SDS),

(a method to infer very recent changes in allele frequencies from contemporary genome sequences). Applied to data from the UK10K Project, SDS measured allele-frequency changes in ancestors of modern Britons during the past ~2000 to 3000 years (this even predates Brexit). They found strong signals of selection at the lactase gene (involved in digestion of milk) and the major histocompatibility complex (involving the immune system), and in favor of blond hair and blue eyes. For polygenic adaptation, recent selection for increased height was discovered to have driven allele-frequency shifts across most of the genome.

Despite selection for protection against schizophrenia, this disorder has persisted and perhaps become even more prevalent — but reasons for this are not known. Many of schizophrenia’s symptoms (i.e. experiencing auditory hal­lucinations, jumbling sentences) involve brain regions tied to speech. Over the course of hominid evolution, the benefits of “ability to speak” might have out­weighed the small risk that genes (involved in language) could malfunction and result in schizophrenia in a small percentage of the population.

Another project described the dissection of environmental factors, mental illnesses, and behavioral traits. Looking at 2,455 DNA samples from individuals at 23 geographical sites across Europe, authors quantified each person’s overall genetic likelihood of conditions (such as autism) and personality traits (such as being extraverted rather than introverted. The scientists then calculated whether that risk was associated with certain environmental factors –– such as amount of rainfall, extremely cold winter temperatures, or prevalence of infectious diseases — exploring the idea that these factors might have been involved in selecting for such human traits. Persons living in parts of Europe with relatively lower winter temperatures were found to be slightly more genetically prone to schizophrenia (or is it just that long, dark nights induce people to drive more alcohol?). It was suggested that, if the genes that helped people to tolerate cold lay close to variants that enhanced risk of schizophrenia, then schizophrenia-related genes could have been inadvertently carried along during evolution as “fellow travelers” from one generation to the next.

Nature 2 Nov 2o17; 551: 15–16 [editorial] and Science 2o16; 354: 760-764 [full article]

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