Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci

NBCS Investigators

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Mammographic density (MD) phenotypes, including percent density (PMD), area of dense tissue (DA), and area of non-dense tissue (NDA), are associated with breast cancer risk. Twin studies suggest that MD phenotypes are highly heritable. However, only a small proportion of their variance is explained by identified genetic variants. METHODS: We conducted a genome-wide association study, as well as a transcriptome-wide association study (TWAS), of age- and BMI-adjusted DA, NDA, and PMD in up to 27,900 European-ancestry women from the MODE/BCAC consortia. RESULTS: We identified 28 genome-wide significant loci for MD phenotypes, including nine novel signals (5q11.2, 5q14.1, 5q31.1, 5q33.3, 5q35.1, 7p11.2, 8q24.13, 12p11.2, 16q12.2). Further, 45% of all known breast cancer SNPs were associated with at least one MD phenotype at p < 0.05. TWAS further identified two novel genes (SHOX2 and CRISPLD2) whose genetically predicted expression was significantly associated with MD phenotypes. CONCLUSIONS: Our findings provided novel insight into the genetic background of MD phenotypes, and further demonstrated their shared genetic basis with breast cancer.

Original languageEnglish (US)
Pages (from-to)27
Number of pages1
JournalBreast cancer research : BCR
Volume24
Issue number1
DOIs
StatePublished - Apr 12 2022

Keywords

  • Breast cancer
  • Genome-wide association study (GWAS)
  • Mammographic density
  • Transcriptome-wide association study (TWAS)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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