Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Magnetic energy powers the corona: how we can understand its 3D storage & release

The coronal magnetic field is the prime driver behind many as-yet unsolved mysteries: solar eruptions, coronal heating, and the solar wind, to name a few. It is, however, still poorly observed and understood. We highlight key questions related to magnetic energy storage, release, and transport in the solar corona, and their relationship to these important problems. We advocate for new and multi-point co-optimized measurements, sensitive to magnetic field and other plasma parameters, spanning from optical to γ-ray wavelengths, to bring closure to these long-standing and fundamental questions. We discuss how our approach can fully describe the 3D magnetic field, embedded plasma, particle energization, and their joint evolution to achieve these objectives