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Chunk #4 — RESULTS — SNPs on 12q21.31 are associated with MD

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The neuronal transporter gene SLC6A15 confers risk to major depression.
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We performed a GWA study in a sample of 353 unipolar depressed German inpatients from the MARS study (Hennings et al., 2009) and 366 screened controls using Illumina 100k and 300k Beadchips (Manhattan plot, see fig. S2). After applying stringent quality control criteria (see methods), 365,676 SNPs entered association analysis. Neither genomic controls nor Eigenstrat showed evidence for population stratification in this sample (fig. S1). The common SNP rs1545843 (MAF=0.41 in controls) on chr12q21.31 showed experiment-wide significance in a recessive mode of inheritance (AA vs. AG+GG) after applying the permutation-based minimum p method for multiple comparison correction over all tested SNPs and genetic models (tab. 1, fig. 1B and fig. S2; N=353/366, nominal p=5.53e-08; OR=2.84 {95% confidence interval 1.92 – 4.21}). Seven additional common SNPs in linkage disequilibrium (LD) with rs1545843 located in a region spanning about 450 kb gave nominal p-values smaller than 5.0e-04 applying the recessive model (tab. 1, fig. 1B and fig. S2). The pairwise r2-values ranged from 0.40 to >0.99 in controls (fig. 2A and fig. S2A) suggesting that all eight SNPs might tag the same