The Association of Common SNPs and Haplotypes in <i>CETP</i> Gene with HDL Cholesterol Levels in Latvian Population

<div><p>The heritability of high-density lipoprotein cholesterol (HDL-C) level is estimated at approximately 50%. Recent genome-wide association studies have identified genes involved in regulation of high-density lipoprotein cholesterol (HDL-C) levels. The precise genetic profile determining heritability of HDL-C however are far from complete and there is substantial room for further characterization of genetic profiles influencing blood lipid levels. Here we report an association study comparing the distribution of 139 SNPs from more than 30 genes between groups that represent extreme ends of HDL-C distribution. We genotyped 704 individuals that were selected from Genome Database of Latvian Population. 10 SNPs from <i>CETP</i> gene showed convincing association with low HDL-C levels (rs1800775, rs3764261, rs173539, rs9939224, rs711752, rs708272, rs7203984, rs7205804, rs11076175 and rs9929488) while 34 SNPs from 10 genes were nominally associated (p<0.05) with HDL-C levels. We have also identified haplotypes from <i>CETP</i> with distinct effects on determination of HDL-C levels. Our conclusion: So far the SNPs in <i>CETP</i> gene are identified as the most common genetic factor influencing HDL-C levels in the representative sample from Latvian population.</p></div

F_ST values and the number of SNPs with significant differences in allele frequencies between the populations from Russia^*.

*<p>Pairwise F_ST values are indicated below the diagonal and the number of SNPs is indicated above it. The abbreviations of populations are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058552#pone-0058552-g001" target="_blank">Figure 1</a>.</p

Principal component analysis of the combined autosomal genotypic data of individuals from Russia and seven European countries (Finnland, Estonia, Latvia, Poland, Czech Republic, Germany [5] and Italia [22]).

<p>The first two PCs are shown. The color legend for the predefined population labels is indicated within the plot. Population designations are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058552#pone-0058552-g001" target="_blank">Figure 1</a>.</p

Summary of ROH statistics of 16 European populations.

*<p>ROH calculated without the thresholds for SNP density and length of the gaps along a ROH tract. The abbreviations of populations are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058552#pone-0058552-g001" target="_blank">Figure 1</a>.</p

ADMIXTURE clustering of individuals from the populations studied.

<p>Results obtained at K = 2 to 5 are shown. Each individual is represented by a vertical line composed of colored segments, in which each segment represents the proportion of an individual’s ancestry derived from one of the K ancestral populations. Individuals are grouped by population (labeled on the bottom of the graph). In addition to populations used in principal component analysis, a Chinese sample (Han Chinese from Beijing <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058552#pone.0058552-The1" target="_blank">[22]</a>) was included. The results at K = 5 are also accompanied by average ancestral proportions by population (*). Population designations are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058552#pone-0058552-g001" target="_blank">Figure 1</a>.</p

Principal component analysis of the autosomal genotypic data of individuals from European Russia.

<p>The first two PCs are shown. Each individual is represented by a sign and the color label corresponding to their self-identified population origin. Population designations are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058552#pone-0058552-g001" target="_blank">Figure 1</a>.</p

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies