Breast cancer risk is influenced by rare coding variants in susceptibility genes such as BRCA1 and many common, mainly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. We report results from a genome-wide association study (GWAS) of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry1. We identified 65 new loci associated with overall breast cancer at p<5x10-8. The majority of credible risk SNPs in the new loci fall in distal regulatory elements, and by integrating in-silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all SNPs in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the utility of genetic risk scores for individualized screening and prevention.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3, 9q31.1) and one for endometrioid EOC (5q12.3). We then meta-analysed the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified an additional three loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a novel susceptibility gene for low grade/borderline serous EOC.

Background Common cancers develop through a multistep process often including inherited susceptibility. Collaboration among multiple institutions, and funding from multiple sources, has allowed the development of an inexpensive genotyping microarray, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers and cancer related traits. Methods The OncoArray can be genotyped using a novel technology developed by Illumina to facilitate efficient genotyping. The consortium developed standard approaches for selecting SNPs for study, for quality control of markers and for ancestry analysis. The array was genotyped at selected sites and with prespecified replicate samples to permit evaluation of genotyping accuracy among centers and by ethnic background. Results The OncoArray consortium genotyped 447,705 samples. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis. Conclusions Results from these analyses will enable researchers to identify new susceptibility loci, perform fine mapping of new or known loci associated with either single or multiple cancers, assess the degree of overlap in cancer causation and pleiotropic effects of loci that have been identified for disease-specific risk, and jointly model genetic, environmental and lifestyle related exposures. Impact Ongoing analyses will shed light on etiology and risk assessment for many types of cancer.

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease1. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10−8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 14% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.

Negative correlations among yield components are wide spread among the major crop plants, particularly under various kinds of environmental stress. The correlations are believed to be developmental rather than genetic per se, and are postulated to be caused by genetically independent components, developing in a sequential pattern, that are free to vary in response to either 1) a limited constant input of metabolites, or 2) an oscillatory input of these substances such that input is limiting at critical stages in the developmental sequence.

The association of genetic distance and heterosis was investigated in dry edible bean (Phaseolus vulgaris L.) and faba bean (Viciafaba L.). Dry bean materials consisted of 28 F2 populations of an 8 × 8 diallel, and their respective parents, grown in eight replications in the field at East Lansing, Mich. in 1981. Faba bean materials comprised the 64 F1's and parents of an 8 × 8 diallel grown in 1975, and 120 populations grown in 1976 como prised of F1's, F2's, and parents of the same diallel, grown in four replications at the Agricultural Research Center at Giza, Egypt. Mahalanobis' D2 was used to estimate genetic distance between parents. Heterosis was measured as deviation from midparent. Correlations in dry beans between heterotic effects and parental distances were positive and highly significant for yield at harvest and for two of the three yield components, namely, number pods/plant and number seeds/pod. No relationship was found for 100‐seed weight. A highly significant positive correlation was obtained for leaf weight. Both significantly positive and negative correlations were found in faba beans for an array of “number” traits related to yield, but heterosis for yield of seed per se in faba beans was not associated with the Mahalanobis D2's

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S U M M A R YThe objective of this study was to identify traits related to growth and yield response under drought stress in the field which would show less variation than yield itself. Experiments were conducted in 1987, at Durango, Mexico and at Michigan, USA. Twenty-six dry bean genotypes were sown under supplementary irrigation and terminal drought stress. Plant samples were taken at 50% flowering, mid-pod-filling and physiological maturity. At both sites, leaf expansion rate and crop growth rate at mid-pod-filling were greatly reduced by drought stress, resulting in significant reductions in total dry matter (DM) above ground and seed yield at physiological maturity. Because of differences in the timing and intensity of the drought stress, the yield components were affected differently at each location. Total DM content at physiological maturity, harvest index and number of pods/m 2 were the only traits positively correlated with yield under stress at both locations. In order to evaluate a group of genotypes for adaptation to drought on the basis of seed yield, the genotypes should be grouped according to their phenological characteristics to stress them evenly.