nandixon
Senior Member
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Although the frequency of most SNPs are similar across ethnic groups, there are many SNPs for which the allelic frequency is significantly different between different ethnic groups.
An SNP that is essentially benign in one ethnic group can be very problematic in another. This can be due, for example, to differences in the frequencies of other SNPs but also epigenetic differences, including differences in methylation due to diet, for example, among numerous other epigenetic possibilities.
Those epigenetic differences are critical and can easily be as important - or more important - than the SNPs themselves, since they can, for example, override an SNP that causes an undesirable loss or gain of enzymatic activity by, for example, increasing or decreasing the expression of the gene in question, thus negating the deleterious effect of the SNP - and making an SNP that causes problems in one ethnic group of less significance in another.
This means that when trying to discover SNPs that may cause or contribute to an illness - especially one like ME/CFS - the appropriate ethnic database of allelic frequencies should be used for comparison with the patient, i.e., a European database for Europeans, an Asian database for Asians, etc.
If this isn't done there is a significant risk of false negative results and futile searching, because: We simply do not know whether the SNPs (if they exist) that may contribute to ME/CFS are ones that fall into the category of SNPs that have a similar allelic frequency across ethnic groups OR into the category of SNPs that have a different allelic frequency across ethnic groups. (Obviously, more false positives will be generated using the appropriate ethnic database and this needs to be considered.)
Importantly, the largest differences in allelic frequencies seem to occur between European and Asian ethnicities.
Thus, when attempting to look for disease-causing SNPs in the largely European or European-descended members of this forum, using the (full) data from the 1000 Genomes Project, for example, is especially problematic - i.e., prone to false negative results - because that database contains a majority of Asian DNA samples. (The percentage of European DNA in that database is only about 20%, the last time I looked.)
If an SNP or SNPs has the potential to cause or contribute to ME/CFS in Europeans, for example, that SNP may be missed when using 1000 Genomes data if it is benign in Asians (for example) yet present at a higher frequency in the Asian population - since it will appear to be more common than it actually is in Europeans. And vice versa, of course.
In summary, the scientific literature is clear that ethnicity can be a critical factor when attempting to narrow down what potential SNP or SNPs might cause or contribute to an illness, and that an ethnically appropriate genetic database should be used to avoid false negative results for SNPs that may be disease-causing/contributing and of lower frequency in one ethnic group but benign and of higher frequency in other ethnic groups.
There are dozens of research articles that have been published that emphasise this. Below are just a handful:
An SNP that is essentially benign in one ethnic group can be very problematic in another. This can be due, for example, to differences in the frequencies of other SNPs but also epigenetic differences, including differences in methylation due to diet, for example, among numerous other epigenetic possibilities.
Those epigenetic differences are critical and can easily be as important - or more important - than the SNPs themselves, since they can, for example, override an SNP that causes an undesirable loss or gain of enzymatic activity by, for example, increasing or decreasing the expression of the gene in question, thus negating the deleterious effect of the SNP - and making an SNP that causes problems in one ethnic group of less significance in another.
This means that when trying to discover SNPs that may cause or contribute to an illness - especially one like ME/CFS - the appropriate ethnic database of allelic frequencies should be used for comparison with the patient, i.e., a European database for Europeans, an Asian database for Asians, etc.
If this isn't done there is a significant risk of false negative results and futile searching, because: We simply do not know whether the SNPs (if they exist) that may contribute to ME/CFS are ones that fall into the category of SNPs that have a similar allelic frequency across ethnic groups OR into the category of SNPs that have a different allelic frequency across ethnic groups. (Obviously, more false positives will be generated using the appropriate ethnic database and this needs to be considered.)
Importantly, the largest differences in allelic frequencies seem to occur between European and Asian ethnicities.
Thus, when attempting to look for disease-causing SNPs in the largely European or European-descended members of this forum, using the (full) data from the 1000 Genomes Project, for example, is especially problematic - i.e., prone to false negative results - because that database contains a majority of Asian DNA samples. (The percentage of European DNA in that database is only about 20%, the last time I looked.)
If an SNP or SNPs has the potential to cause or contribute to ME/CFS in Europeans, for example, that SNP may be missed when using 1000 Genomes data if it is benign in Asians (for example) yet present at a higher frequency in the Asian population - since it will appear to be more common than it actually is in Europeans. And vice versa, of course.
In summary, the scientific literature is clear that ethnicity can be a critical factor when attempting to narrow down what potential SNP or SNPs might cause or contribute to an illness, and that an ethnically appropriate genetic database should be used to avoid false negative results for SNPs that may be disease-causing/contributing and of lower frequency in one ethnic group but benign and of higher frequency in other ethnic groups.
There are dozens of research articles that have been published that emphasise this. Below are just a handful:
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