Several genetic models were tested for SNPs that were polymorphic in this population. Individuals in the sample were treated as cases or controls, with cases being the particular hair colour phenotype under study and controls being the rest of the population. The Odds Ratio (OR) is reported for the effect that the minor allele or particular genotype being considered has on the case phenotype. An odds ratio of 1 means that this allele or genotype is equally likely to be found in both cases and controls. An odds ratio greater than one means that this particular allele or genotype is more likely to be found in the cases than in the controls. An odds ratio less than one means that this particular allele or genotype is more likely to be found in the controls than in the cases (this is the case when the major allele is associated with the phenotype being considered).
The SNP being considered, the minor allele, the odds ratio, the gene that the SNP can be found in and the amino acid substitution it causes are reported for each of the models tested (Table 7.7 Table 7.15). In Tables 7.6 to 7.14; N equals the number of cases, D represents the minor allele and d represents the major allele.
The whole population was considered first. It is well known that variations in the gene MC1R contribute to Red hair colour [18], so the first allelic test used individuals in Cluster 1 (Red) as cases (Table 7.7). Table 7.8 shows the SNPs that were found to be significantly associated with Cluster 2 (Blonde/Fair) at the allelic level.
Table 7.7 SNPs found to be significantly associated with LL5 Red (Cluster 1) at the α = 0.1 level for the allelic model (N = 8)
D vs. d
SNP Minor Allele OR Gene Amino Acid
Change
Table 7.8 SNPs found to be significantly associated with LL5 Fair/Blonde (Cluster 2) at the α =
0.1 level for the allelic model (N = 32)
D vs. d
SNP Minor Allele OR Gene Amino Acid
Change
rs16876571 A 7.7 DTNBP1 H297Y
rs2276288 A 1.6 MYO7A C1628S
The following tests use Cluster 2 (Fair/Blonde) as the cases for a dominant model of association (Table 7.9) and a recessive model (Table 7.10).
Table 7.9 SNPs found to be significantly associated with LL5 Fair/Blonde (Cluster 2) at the α =
0.1 level for the dominant model (N = 32)
DD/Dd vs. dd
SNP Minor Allele OR Gene Amino Acid
Change
rs16876571 A 8.0 DTNBP1 H297Y
rs2276288 A 2.4 MYO7A C1628S
rs1805007 T 2.1 MC1R R151C
Table 7.10 SNPs found to be significantly associated with LL5 Fair/Blonde (Cluster 2) at the α =
0.1 level for the recessive model (N = 32)
DD vs. Dd/dd
SNP Minor Allele OR Gene Amino Acid
Change
rs1800422 A 3.1 TYR R402Q
Since the variations in MC1R leading to red hair are well known and can already be tested for [14, 18, 37-41, 108], additional tests were conducted with the eight individuals from Cluster 1 (Red) removed from the population. This was done to independently test for associations with Fair/Blonde hair colour at the allelic level (Table 7.11) and with a dominant (Table 7.12) or recessive model (Table 7.13).
Table 7.11 SNPs found to be significantly associated with LL5 Fair/Blonde (Cluster 2) at the α =
0.1 level for the allelic model with Cluster 1 removed (N = 32)
D vs. d
SNP Minor Allele OR Gene Amino Acid
Change
rs16876571 A 7.3 DTNBP1 H297Y
rs1805007 T 2.3 MC1R R151C
rs2276288 A 1.7 MYO7A C1628S
rs1800422 A 1.7 TYR R402Q
Table 7.12 SNPs found to be significantly associated with LL5 Fair/Blonde (Cluster 2) at the α =
0.1 level for the dominant model with Cluster 1 removed (N = 32)
DD/Dd vs. dd
SNP Minor Allele OR Gene Amino Acid
Change
rs16876571 A 7.6 DTNBP1 H297Y
rs1805007 T 2.6 MC1R R151C
rs2276288 A 2.4 MYO7A C1628S
Table 7.13 SNPs found to be significantly associated with LL5 Fair/Blonde (Cluster 2) at the α =
0.1 level for the recessive model with Cluster 1 removed (N = 32)
DD vs Dd/dd
SNP Minor Allele OR Gene Amino Acid
Change
Tests for genetic associations with LL5 Cluster 5 (dark hair) were conducted to see if any SNPs had the effect of contributing to darker hair colours and may indicate an opposing process than that which contributes to light hair colours. Table 7.14 and Table 7.15 show the associations found in an allelic and a dominant model. Three SNPs showed associations with LL5 Cluster 5 (Dark) and all were different SNPs than had been associated with Red or Blonde/Fair hair colour (and not simply the opposite allele). However; two SNPs were in ATP7B, a gene that had previously shown a different SNP to be associated with Blonde/Fair hair (See Table 7.10).
Table 7.14 SNPs found to be significantly associated with LL5 Dark (Cluster 5) at the α = 0.1
level for the allelic model (N = 86)
D vs d
SNP Minor Allele OR Gene Amino Acid
Change
rs16891982 C 3.86 MATP L374F
Table 7.15 SNPs found to be significantly associated with LL5 Dark (Cluster 5) at the α = 0.1
level for the dominant model (N = 86)
DD/Dd vs. dd
SNP Minor Allele OR Gene Amino Acid
Change
rs16891982 C 3.46 MATP L374F
rs1801243 G 0.49 ATP7B S406A