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Identification of nine novel loci related to hematological traits in a Japanese population.
Physiological Genomics 2018 September 2
Recent genome-wide association studies have identified various genetic variants associated with hematological traits. Although it is possible that quantitative data of hematological traits are varied among the years examined, conventional genome-wide association studies have been conducted in a cross-sectional manner that measures traits at a single point in time. To address this issue, we have traced blood profiles in 4,884 Japanese individuals who underwent annual health check-ups for several years. In the present study, longitudinal exome-wide association studies were conducted to identify genetic variants related to 13 hematological phenotypes. The generalized estimating equation model showed that a total of 67 single nucleotide polymorphisms (SNPs) were significantly [false discovery rate (FDR) of <0.01] associated with hematological phenotypes. Of the 67 SNPs, nine SNPs were identified as novel hematological markers: rs4686683 of SENP2 for red blood cell count (FDR = 0.008, P = 5.5 × 10-6 ); rs3917688 of SELP for mean corpuscular volume (FDR = 0.005, P = 2.4 × 10-6 ); rs3133745 of C8orf37-AS1 for white blood cell count (FDR = 0.003, P = 1.3 × 10-6 ); rs13121954 at 4q31.2 for basophil count (FDR = 0.007, P = 3.1 × 10-5 ); rs7584099 at 2q22.3 (FDR = 2.6 × 10-5 , P = 8.8 × 10-8 ), rs1579219 of HCG17 (FDR = 0.003, P = 2.0 × 10-5 ), and rs10757049 of DENND4C (FDR = 0.008, P = 5.6 × 10-5 ) for eosinophil count; rs12338 of CTSB for neutrophil count (FDR = 0.007, P = 2.9 × 10-5 ); and rs395967 of OSMR-AS1 for monocyte count (FDR = 0.008, P = 3.2 × 10-5 ).
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