Happened to look online for "GWAS Schizophrenia" and found this study. Only read a little but I felt there were parallels with ME/CFS GWAS "journey" ---. Interesting that there were two GWAS strategies - "The two groups have followed complementary paths in their study of schizophrenia genetics. Since 2009, the PGC team has conducted increasingly larger genome-wide association studies cataloging common genetic variations called single nucleotide polymorphisms (or SNPs) that contribute to schizophrenia risk. The SCHEMA (SCHizophrenia Exome Meta-Analysis) Consortium — which came together in 2017 — focuses on the exome, the nearly two-percent of the genome that encodes proteins. Specifically, the SCHEMA Consortium looked for variants that would either knock out or markedly alter a gene’s ability to produce functioning proteins." https://www.broadinstitute.org/news...d-genome-regions-influence-schizophrenia-risk
This is the kind of study that could be useful in ME/CFS. In my own genome I've found about 50-100 of monoallelic mutations that are predicted to be severe enough to affect the protein. Most of these are probably being tolerated but they could act as risk factors under specific conditions and I suspect there's at least one that dramatically increases the risk of ME/CFS or a similar illness.
Replying to my own post - seems the underlying logic of focusing (GWAS) on the exome is that it provides direct research targets "Models carrying genetic variants like these — and the protein alterations they produce — are easier to create in the lab than those with more common disease-related variants that occur in non-coding parts of the genome and that have unclear effects on protein function." Bipolar article - https://www.broadinstitute.org/news...t-strong-genetic-risk-factor-bipolar-disorder
For example one of variants I have, one where loss of protein function on that allele is nearly certain according to prediction tools, has to do with cell motility, and in particular phagocytosis (the removal of debris, dead or infected cells). Prusty believes inefficient clearing of cell debris contributes to the illness. One could easily fit such a mutation into a model of how ME/CFS arises. A study that looked for such rare very likely damaging mutations could find out whether mutations in genes involved in phagocytosis are overrepresented among ME/CFS patients or not.
