Large-scale genotyping identifies 41 new loci associated with breast cancer risk

Abstract

Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ~9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10−8). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility.

Polygenic risk of Parkinson disease is correlated with disease age at onset

“…In accordance with the pattern seen in studies of other complex diseases shown to have a polygenic signal,18, 24, 25, 26 restricting our analysis to SNPs that met the lowest association test probability value thresholds ( p T ) in the discovery sample ( p T  < 10 −4 , p T  < 10 −3 , p T  < 0.01, p T  < 0.05) did not identify a systematic significant inflation in the polygenic scores of the PD cases of the replication samples ( p  > 0.05). Rather, our most significant evidence was observed when SNPs with p T  ≤ 0.5 in the UK sample were included where probability values for a significant inflation in the polygenic scores ranged between 4.42 × 10 −4 and 8.22 × 10 −5 (see Table 1).…”

An intergenic risk locus containing an enhancer deletion in 2q35 modulates breast cancer risk by deregulating IGFBP5 expression

“…Genotype data for replication were derived from 11 breast cancer GWAS based on populations of European ancestry, together with 41 additional case-control studies from populations of European ancestry participating in the Breast Cancer Association Consortium (2). The 11 GWAS were genotyped by using a variety of different platforms, while the 41 additional case-control studies were genotyped using a custom array (iCOGS).…”

“…Several genome wide association studies (GWAS) have identified the 2q35 region as associated with breast cancer risk (2)(3)(4)(5). Recent work has revealed the complexity of chromatin interactions in the 2q35 region (6) and its involvement in transcriptional regulation of neighbouring gene, IGFBP5 (MIM: 146734).…”

“…The association of the most well studied variant, rs13387042, was recently discovered to be driven by another causal variant in the same LD block, rs4442975 (5). The other independent cancer associated variant, rs16857609, lies in its own LD block telomeric to the other variants (2).…”

A family-based, genome-wide association study of young-onset breast cancer: inherited variants and maternally mediated effects

“…All 18 were located near SNPs that had been previously identified as susceptibility variants for breast cancer across a broader age range. Given the paucity of GWAS of young-onset breast cancer, it is not yet possible to conduct pooled, consortia-based analyses at a size comparable to some of the recent breast cancer GWAS (for example, Michailidou et al 11 or Garcia-Closas et al 12 ).…”