1) An average risk of type 2 DM. The rs9465871 SNP can have a C or T at this position (it's also worth
noting that the SNPs on this Affy chip has been chosen for being bi-allelic even though most SNPs are
tri-allelic). The Welcome Trust Nature paper has the C allele as the one being associated with increased
risk. The T allele is the more common one in the general population. You are heterozygous and have a
C on one DNA strand and a T on the other DNA strand at this position. This could mean you have an
average or slightly increased risk of type 2 DM (as high risk would be C/C, average would be T/T) but
it hasn't been studied well enough yet. This SNP is on 10q25 (which is the long arm of chromosome
10) and is believed to be in LD with the CDKAC1 gene. Though they get a statisitically significant p-
value of around 1X10 e-6, to put all this in proper perspective, the control group had the C allele in
17.8% of people and 21.8% of cases had the C allele.
2) I've looked at 2 of their strongest SNPs for RA in this paper. For rs6679677 (in LD with the PTPN22
gene on 11p13), you could have an A or C in this position. A is associated with increased risk (with a
frequency of 9.6% in controls vs. 16.8% in cases). You are homozygous with C/C on both strands at
this position. Does this mean you are at lower risk? That is unclear but you don't have the risk allele at
this position. What if we look at another RA SNP? At rs6457617, you can have a C or a T; and a T at
this position has been associated with increased risk of RA according to this study. Here you are in the
same situation as in #1 with DM2: you are heterozygous for both. Invariably, people will have a
combination of risk and (as we discover them) protective alleles.
3) The study came up with one strong SNP association for CAD. At rs1333049, you can have a C or G.
C is the risk allele and you are homozygous for C/C. So a potentially increased risk for CAD at this one
position. Again, let's put it in perspective, p-values are around 1X10e-13 but the frequency of the C
allele in controls was 47.4% vs. 55.4% in cases -so you've got a lot of controls with the same genotype
and we know nothing of protective alleles (or detrimental ones for CAD) in your other genes.
Furthermore, the SNP is supposedly in LD with the following genes: CDKN2A, CDKN2B, DMRTA1,
and MTAP. It would be better to have an known mutations in a coding region of one of these genes,
(particularly if it were one invlolved in cholesterol metabolism or vessel diameter or inflammation or
thrombus formation) and if that specific mutation were known to be associated with an increased risk