Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer.

Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.BCAC is funded by Cancer Research UK (C1287/A10118, C1287/A12014) and by the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). Genotyping on the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710, C8197/A16565), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer program and the Ministry of Economic Development, Innovation and Export Trade of Quebec, grant PSR-SIIRI-701. Combination of the GWAS data was supported in part by the US National Institutes of Health (NIH) Cancer Post-Cancer GWAS initiative, grant 1 U19 CA148065-01 (DRIVE, part of the GAME-ON initiative). For a full description of funding and acknowledgments, see the Supplementary Note.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.324

Vitamin D status and clinical implications in the adult population of Malaysia: A position paper by the Malaysian Vitamin D Special Interest Group

Purpose: Vitamin D deficiency and insufficiency is common among populations globally, and in Asia and Malaysia. The purpose of this Position Paper is to propose recommendations for both clinicians and non-clinicians to promote vitamin D sufficiency in Malaysian adults. Formation of a national multisector, multidisciplinary alliance is also proposed to progress initiatives relating to safe sun exposure, adequate vitamin D intake through food fortification, and vitamin D supplementation for high-risk groups. Methods: Literature reviews were undertaken to inform summaries of the following: vitamin D status globally and in Asian and Malaysian populations, vitamin D status among individuals with common medical conditions, and current recommendations to achieve vitamin D sufficiency through sun exposure, food intake and supplementation. Recommendations were based on the findings of the literature reviews, recent European guidance on vitamin D supplementation, the 2018 road map for action on vitamin D in low- and middle-income countries, and research recommendations proposed by the Malaysian Ministry of Health in 2017. Results: Recommendations on assessment of vitamin D in the adult Malaysian population include using serum or plasma 25-hydroxyvitamin D concentration as a biomarker, widespread participation by Malaysian laboratories in the Vitamin D Standardization Program, adoption of the US Endocrine Society definitions of vitamin D deficiency and insufficiency, and development of a comprehensive nationwide vitamin D status study. Specific high-risk groups are identified for vitamin D assessment and recommendations relating to loading doses and ongoing management are also made. Conclusion: This Position Paper provides individual clinicians and national stakeholder organisations with clear recommendations to achieve vitamin D sufficiency in the adult population of Malaysia

Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

Genome wide association studies (GWAS) and large scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ~14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS comprising of 15,748 breast cancer cases and 18,084 controls, and 46,785 cases and 42,892 controls from 41 studies genotyped on a 200K custom array (iCOGS). Analyses were restricted to women of European ancestry. Genotypes for more than 11M SNPs were generated by imputation using the 1000 Genomes Project reference panel. We identified 15 novel loci associated with breast cancer at P<5×10−8. Combining association analysis with ChIP-Seq data in mammary cell lines and ChIA-PET chromatin interaction data in ENCODE, we identified likely target genes in two regions: SETBP1 on 18q12.3 and RNF115 and PDZK1 on 1q21.1. One association appears to be driven by an amino-acid substitution in EXO1