Common genetic variation and novel loci associated with volumetric mammographic density View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Judith S. Brand, Keith Humphreys, Jingmei Li, Robert Karlsson, Per Hall, Kamila Czene

ABSTRACT

BACKGROUND: Mammographic density (MD) is a strong and heritable intermediate phenotype of breast cancer, but much of its genetic variation remains unexplained. METHODS: We conducted a genetic association study of volumetric MD in a Swedish mammography screening cohort (n = 9498) to identify novel MD loci. Associations with volumetric MD phenotypes (percent dense volume, absolute dense volume, and absolute nondense volume) were estimated using linear regression adjusting for age, body mass index, menopausal status, and six principal components. We also estimated the proportion of MD variance explained by additive contributions from single-nucleotide polymorphisms (SNP-based heritability [h2SNP]) in 4948 participants of the cohort. RESULTS: In total, three novel MD loci were identified (at P < 5 × 10- 8): one for percent dense volume (HABP2) and two for the absolute dense volume (INHBB, LINC01483). INHBB is an established locus for ER-negative breast cancer, and HABP2 and LINC01483 represent putative new breast cancer susceptibility loci, because both loci were associated with breast cancer in available meta-analysis data including 122,977 breast cancer cases and 105,974 control subjects (P < 0.05). h2SNP (SE) estimates for percent dense, absolute dense, and nondense volume were 0.29 (0.07), 0.31 (0.07), and 0.25 (0.07), respectively. Corresponding ratios of h2SNP to previously observed narrow-sense h2 estimates in the same cohort were 0.46, 0.72, and 0.41, respectively. CONCLUSIONS: These findings provide new insights into the genetic basis of MD and biological mechanisms linking MD to breast cancer risk. Apart from identifying three novel loci, we demonstrate that at least 25% of the MD variance is explained by common genetic variation with h2SNP/h2 ratios varying between dense and nondense MD components. More... »

PAGES

30

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s13058-018-0954-6

    DOI

    http://dx.doi.org/10.1186/s13058-018-0954-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1103409362

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29665850


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