We conducted a meta-analysis of genome-wide association studies of systolic (SBP) and diastolic (DBP) blood pressure in 19,608 subjects of East Asian ancestry from the AGEN-BP consortium followed by de novo genotypingin 2 stages of replication involving 10,518 and 20,247 East Asian samples. We identified novel genome-wide significant (P < 5 × 10−8) associations between SBP or DBP and variants at four novel loci: ST7L-CAPZA1, FIGN-GRB14, ENPEP, and NPR3, as well as a novel variant near TBX3. Except for NPR3, all novel findings were significantly replicated for SBP or DBP in independent samples. Sevenloci previously reported in populations of European descent were confirmed. On 12q24.13, we observed an ethnic specific association(implicating rs671 at the ALDH2 locus as the causal variant) that affected SBP, DBP and multiple traits related to coronary artery disease. These findings provide novel insights into blood pressure regulation and potential targets for intervention.

Runx2 (runt-related transcription factor 2, also known as Cbfa1, Osf2 and AML3) is essential for bone development in mice, and mutations in RUNX2 are found in 65-80% of individuals with cleidocranial dysplasia. Although all Runx family members can interact with Cbfbeta (core-binding factor b, encoded by Cbfb), a role for Cbfbeta in bone development has not been demonstrated owing to lethality in Cbfb(-/-) mouse embryos at 12.5 days post coitum (d.p.c.) from hemorrhages and lack of definitive hematopoiesis. Using a 'knock-in' strategy, we generated mouse embryonic stem (ES) cells that express Cbfb fused in-frame to a cDNA encoding green fluorescent protein (GFP). Cbfb(+/GFP) mice had normal life spans and appeared normal, but Cbfb(GFP/GFP) pups died within the first day after birth. The Cbfb(GFP/GFP) mice exhibited a delay in endochondral and intramembranous ossification as well as in chondrocyte differentiation, similar to but less severe than delays observed in Runx2(-/-) mice. We demonstrate that Cbfbeta is expressed in developing bone and forms a functional interaction with Runx2, and that Cbfb(GFP) is a hypomorphic allele. The fusion allele maintains sufficient function in hematopoietic cells to bypass the early embryonic lethality, and identifies a new role for Cbfb in bone development. Our findings raise the possibility that mutations in CBFB may be responsible for some cases of cleidocranial dysplasia that are not linked to mutations in RUNX2.

The first version of the Standard PREanalytical Code (SPREC) was developed in 2009 by the International Society for Biological and Environmental Repositories (ISBER) Biospecimen Science Working Group to facilitate documentation and communication of the most important preanalytical quality parameters of different types of biospecimens used for research. This same Working Group has now updated the SPREC to version 2.0, presented here, so that it contains more options to allow for recent technological developments. Existing elements have been fine tuned. An interface to the Biospecimen Reporting for Improved Study Quality (BRISQ) has been defined, and informatics solutions for SPREC implementation have been developed. A glossary with SPREC-related definitions has also been added.

IntroductionAlthough approximately 25 common genetic susceptibility loci have been identified to be independently associated with breast cancer risk through genome-wide association studies (GWAS), the genetic risk variants reported to date only explain a small fraction of the heritability of breast cancer. Furthermore, GWAS-identified loci were primarily identified in women of European descent.MethodsTo evaluate previously identified loci in Korean women and to identify additional novel breast cancer susceptibility variants, we conducted a three-stage GWAS that included 6,322 cases and 5,897 controls.ResultsIn the validation study using Stage I of the 2,273 cases and 2,052 controls, seven GWAS-identified loci [5q11.2/MAP3K1 (rs889312 and rs16886165), 5p15.2/ROPN1L (rs1092913), 5q12/MRPS30 (rs7716600), 6q25.1/ESR1 (rs2046210 and rs3734802), 8q24.21 (rs1562430), 10q26.13/FGFR2 (rs10736303), and 16q12.1/TOX3 (rs4784227 and rs3803662)] were significantly associated with breast cancer risk in Korean women (Ptrend < 0.05). To identify additional genetic risk variants, we selected the most promising 17 SNPs in Stage I and replicated these SNPs in 2,052 cases and 2,169 controls (Stage II). Four SNPs were further evaluated in 1,997 cases and 1,676 controls (Stage III). SNP rs13393577 at chromosome 2q34, located in the Epidermal Growth Factor Receptor 4 (ERBB4) gene, showed a consistent association with breast cancer risk with combined odds ratios (95% CI) of 1.53 (1.37-1.70) (combined P for trend = 8.8 × 10-14).ConclusionsThis study shows that seven breast cancer susceptibility loci, which were previously identified in European and/or Chinese populations, could be directly replicated in Korean women. Furthermore, this study provides strong evidence implicating rs13393577 at 2q34 as a new risk variant for breast cancer.