I'm new here, but I'm hoping you're still reading through these notes! I'm new to the SNP world as well and and am confused about COMT, based on 23andme data. 1. If we have rs4633 (H62H) CC and rs4680 (V158M) GG, does that mean that they counteract each other? Is H62H CC a slow version and V158M GG a fast version? 2. Why would wild type COMT V158M (rs4680) GG and H62H (rs4633) CC be associated with low activity in haplotype II? I thought they were "normal" activity alleles? We have rs6269 AG, rs4646312 CT, rs4633 CC and rs4680 GG. Would that be haplotype II (or do you need to be homozygous for all 4?)? If so, does that mean we should avoid methyl donors because COMT is too slow? 3. We also have CBS A360A (AA), which supposedly suggests avoiding methyl donors. But then MTHFR A1298C (GT) and MTHFR P39P (AG) suggest to add them, as do MTRR A66G (AG) and MTRR C524T (CT) and MTR rs1805087 (AG). Very confusing. How do you know which SNPs are stronger than others? 4. Are there any blood tests that can tell you if your COMT is working properly, or whether you should take or avoid methyl donors? We are getting tested this weekend for pyroluria and Lyme disease among other things and I want to cover our bases. Thanks everyone!