6 research outputs found
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
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 x 10(-20)), ER-negative BC (P = 1.1 x 10(-13)), BRCA1-associated BC (P = 7.7 x 10(-16)) and triple negative BC (P-diff = 2 x 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P = 2 x 10(-3)) and ABHD8 (PPeer reviewe
Mental Health and Ideals of Citizenship: Patient Care at St. Elizabeths Hospital in Washington, D.C., 1903--1962
367 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2010.The post-World War II era witnessed important changes in both psychiatrists' vision of U.S. citizenship and the institutional culture at St. Elizabeths. Physicians took an increasingly liberal view of race relations under Winfred Overholser, who succeeded White as superintendent in 1937 and was prompted by national developments to integrate the hospital in 1954. These same psychiatrists promoted a restrictive domestic ideal for their female patients, in spite of the fact that middle-class married women were entering the labor market in unprecedented numbers. Physicians charted a cautious middle path in debates on homosexuality, maintaining that same-sex desires signified deep psychological maladjustment even as they protested policies criminalizing consensual sexual contact between adults. These developments occurred in the context of a general liberalization of institutional culture in the postwar decades. Through their own efforts as well as through innovations in clinical psychiatry, patients in the 1940s and 1950s found new opportunities for self-expression and began to articulate a novel sense of shared identity. By the time the major tranquilizers appeared, the appropriateness of long-term custodial care for psychologically-impaired men and women had already come into question.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD
The Efficacy of Combined Therapeutic Protocol of Large-Amplitude Movement, Exercise, and Balance Training on Patients with Parkinson\u27s Disease
Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
10.1038/ncomms12675NATURE COMMUNICATIONS7