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Fig. 2 | Molecular Neurodegeneration

Fig. 2

From: Proteo-genomics of soluble TREM2 in cerebrospinal fluid provides novel insights and identifies novel modulators for Alzheimer’s disease

Fig. 2

Association results of CSF sTREM2 at chromosome 11. A LocusZoom plots at chromosome 11 in European ancestry (EURs) for the sentinel SNP rs72918674 and the secondary signal rs10897026 after conditioning on the sentinel SNP. X-axis depicts genomic coordinates at chromosome 11 and y-axis denotes the negative log10-transformed P value for each genetic variant. B Linkage disequilibrium (LD) heatmap of chromosome 11 SNPs in EURs and non-EURs. C Forest plots of effect size estimates by cohort for rs72918674 (MS4A6A intron), rs10897026 (MS4A4A intron), rs583791 (MS4A6A, p.A112T) and rs6591561 (MS4A4A, p.M178V). Heterogeneity P is 0.36 for rs72918674, 0.41 for rs583791, 0.77 for rs10897026, and 0.79 for rs6591561 respectively. D Summary of association results of two independent SNPs and 6 missense variants in the MS4A gene region from EURs. SNP references single-nucleotide polymorphism and rsID denotes reference SNP cluster ID (rsID), according to dbSNP build 155. Gene is annotated based on Ensembl Variant Effect Predictor (VEP) release 106. Annotation is the definition of identified SNP as Top Hit, Secondary, or amino acid changes. N is the sample size in GWAS of European (EURs) samples. β in EURs is effect estimated in EURs samples. P in EURs is two-sided raw P values in EURs samples. β in non-EURs is effect estimated in non-European (non-EURs) samples. P in non-EURs is two-sided raw P values in non-EURs samples. E Effect of epistasis between rs583791 (MS4A6A, p.A112T) and rs6591561 (MS4A4A, p.M178V) on CSF sTREM2 levels and Log of Alzheimer’s disease (AD) Odds ratio. X-axis is dosage of rs583791 (MS4A6A, p.A112T) coded based on the copy of C allele. Y-axes are Z-score of CSF sTREM2 and Log of AD Odds ratio. The color is based on the dosage of rs6591561 (MS4A4A, p.M178V) coded based on the copy of G allele. The effect allele is T for rs72918674, C for rs583791, G for rs6591561, and C for rs10897026. The association of the first variant rs583791 is much stronger in individuals with CC genotype of the second variant rs6591561, as shown in the steep black line, when compared to that for those with TT genotype

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Molecular Neurodegeneration

ISSN: 1750-1326