A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Replication data for: The Strategic Timing of Position Taking in Congress: A Study of the North American Free Trade Agreement

A critical element of decision making is the timing of choices political actors make; often when a decision is made is as critical as the decision itself. We posit a dynamic model of strategic position announcement based on signaling theories of legislative politics. We suggest that members who receive clear signals from constituents, interest groups, and policy leaders will announce their positions earlier. Those with conflicting signals will seek more information, delaying their announcement. We test several expectations by examining data on when members of the House of Representatives announced their positions on the North American Free Trade Agreement. We also contrast the timing model with a vote model, and find that there are meaningful differences between the factors influencing the timing of position announcements and vote choice. Our research allows analysts to interpret the process leading up to the House action and the end state of that process