Top 10 SNPs within <i>MERTK</i> associated with Multiple Sclerosis susceptibility.

<p>Top 10 SNPs within <i>MERTK</i> associated with Multiple Sclerosis susceptibility.</p

SNPs within <i>MERTK</i> define both risk and protective haplotypes associated with MS susceptibility.

<p>28 SNPs within the <i>MERTK</i> gene form a single block of very high LD (D'>0.99, LOD≥2). The five most frequent haplotypes (population frequency >1%) are shown in this schematic, along with the <i>p</i>-value of association of each haplotype with MS susceptibility as determined using a Chi-square test. Arrowhead indicates the haplotype-tagging allele of rs13414207 in haplotype 5. The alleles presented for rs17174870 are inferred from data obtained from sequencing the opposite strand but are presented as CT to maintain consistency with the remainder of the study.</p

Results of the association testing for variants identified in <i>MERTK</i>.

<p>Results of the association testing for variants identified in <i>MERTK</i>.</p

Gene model association of rs13414207 with Multiple Sclerosis.

<p>Gene model association of rs13414207 with Multiple Sclerosis.</p

The haplotype structure of variants identified in <i>MERTK</i>.

<p>The 52 variants in <i>MERTK</i> genotyped for association with MS susceptibility fall into 4 separate blocks. Haplotype blocks are connected with thick lines if connections are observed in >10% samples and thin lines if connections are observed in >1% samples. A schematic of the <i>MERTK</i> gene is shown underneath indicating the relationship of the blocks to the physical structure of <i>MERTK</i>. The haplotypes coloured in red are significantly associated with MS susceptibility (p<0.05) and the haplotype coloured in blue is associated with protection (p<0.05). The <i>p</i>-value of association was determined using a Chi-square test. #This variant represents a tri-nucleotide in-del (T/- = TGG; -)</p

Summary of variants identified in <i>MERTK</i>.

<p>Summary of variants identified in <i>MERTK</i>.</p

Individuals used for resequencing of <i>MERTK</i>.

<p>Individuals used for resequencing of <i>MERTK</i>.</p

Disease course is altered in the presence of <i>MERTK</i> susceptibility-associated variants.

<p>Individuals initially presenting with a relapsing-remitting course of MS were stratified by both <i>DR15</i> status and genotype at rs7422195. (A) In the presence of the minor (A) allele of rs7422195, <i>DR15</i> negative individuals (n = 370) showed a strong trend towards increased probability of progression (<i>p</i> = 0.07) (B) In the presence of the major (G) allele of rs7422195 <i>DR15</i> homozygous individuals (n = 68) showed a strong trend towards increased probability of progression (<i>p =</i> 0.081)</p

A low-frequency SNP within <i>MERTK</i> is significantly associated with MS susceptibility.

<p>124 SNPs on chromosome 2 were directly genotyped in 3268 MS cases and 3579 controls. (A) The negative log of the unadjusted <i>p</i>-value of each SNP is plotted against the relative position on chromosome 2, with a schematic of the gene structures shown underneath (B). Two SNPs, both within <i>MERTK</i>, reach significance using the Sidak adjustment for multiple testing at a nominal α = 0.05. Association <i>p</i>-values were determined using a Chi-square test. (C) Schematic of the pattern of LD across the whole region, with a large single block of high LD (D'>0.99), including the whole of the <i>MERTK</i> gene, highlighted with a red triangle.</p

Association of <i>MERTK</i> SNPs in populations stratified by <i>DR15</i> status.

<p>Association of <i>MERTK</i> SNPs in populations stratified by <i>DR15</i> status.</p