PMC:3480676 / 7682-10411
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3480676","sourcedb":"PMC","sourceid":"3480676","source_url":"https://www.ncbi.nlm.nih.gov/pmc/3480676","text":"Discussion\nIn this study, we performed a genomewide scan for pulse rate and identified 3 loci accounting for the variation in pulse rate. Two of 3 loci were previously reported and replicated once again in an independent HEXA-shared cohort. The other one (rs2892767) near GJA1 was previously implicated for its association with pulse rate but was not chosen for the replication study, since the SNP did not meet the selection criteria in the discovery stage [5]. In the present study, SNP rs2892767 near GJA1 was taken forward to the replication study using the independent dataset from the HEXA-shared cohort and was nicely confirmed for its association with pulse rate.\nTwo SNPs, rs2892767 near GJA1 and rs12110693 near LOC644502, are 408 kb apart from each other and are located in a separate LD, indicating that both are independent SNPs. The independence between both SNPs was further tested by conditional analyses. We performed multiple linear regression analyses, conditioning the SNPs to each other to find a significantly stronger proxy for pulse rate. However, no dramatic decrease in statistical significance was observed, and no interaction was found between rs2892767 and rs12110693 (Table 3). These results further validate that the 2 SNPs are independent of each other.\nGap junctions are thought to have a crucial role in the synchronized contraction of the heart and in embryonic development. It is also known that gap junctions, clusters of cell-to-cell channels composed of connexins, mediate the orderly spread of electrical excitation throughout the heart [10]. The GJA1-encoding protein has been reported to be involved in the development and function of the heart by allowing direct cell-to-cell exchange of molecules, which mediate multiple signaling events [11]. Mutations in GJA1 cause Mendelian inherited hypoplastic left heart syndrome [12]. Cho et al. [5] previously reported the same locus near GJA1 to be responsible for pulse rate without evidence of replication. In the present study, we successfully replicated the locus in an independent replication study.\nAs indicated from the functional role of GJA1, it is a strong candidate gene for pulse rate. Thus, further efforts, such as fine mapping or imputation based on large-scale sequencing data near rs2892767 on 6q22.31, would reveal the causal variant of this locus. In addition, functional studies for GJA1 would be worthwhile to facilitate a full understanding of its biological role in pulse rate.\nOur study was relatively underpowered to discover additional novel loci and demonstrated that large-scale genomewide meta-analysis comprising hundreds of thousands samples is required for understanding the missing heritability of pulse rate.","divisions":[{"label":"Title","span":{"begin":0,"end":10}}],"tracks":[{"project":"2_test","denotations":[{"id":"23105937-19396169-44845705","span":{"begin":459,"end":460},"obj":"19396169"},{"id":"23105937-19615768-44845706","span":{"begin":1578,"end":1580},"obj":"19615768"},{"id":"23105937-7715640-44845707","span":{"begin":1783,"end":1785},"obj":"7715640"},{"id":"23105937-20639392-44845708","span":{"begin":1865,"end":1867},"obj":"20639392"},{"id":"23105937-19396169-44845709","span":{"begin":1882,"end":1883},"obj":"19396169"}],"attributes":[{"subj":"23105937-19396169-44845705","pred":"source","obj":"2_test"},{"subj":"23105937-19615768-44845706","pred":"source","obj":"2_test"},{"subj":"23105937-7715640-44845707","pred":"source","obj":"2_test"},{"subj":"23105937-20639392-44845708","pred":"source","obj":"2_test"},{"subj":"23105937-19396169-44845709","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#9397ec","default":true}]}]}}