Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. The trans-ancestral genomic architecture of glycemic traits

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Genetic analyses identify widespread sex-differential participation bias

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Large-scale association analyses identify host factors influencing human gut microbiome composition

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Mendelian randomisation study of smoking exposure in relation to breast cancer risk

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Detection and characterization of lung cancer using cell-free DNA fragmentomes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • kConFab Investigators
Vis graf over relationer

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype 1–3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10 −8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.

OriginalsprogEngelsk
TidsskriftNature Genetics
Vol/bind52
Udgave nummer6
Sider (fra-til)572-581
Antal sider10
ISSN1061-4036
DOI
StatusUdgivet - jun. 2020

ID: 61974859