Please use this identifier to cite or link to this item: https://doi.org/10.1186/s13058-018-0954-6
Title: Common genetic variation and novel loci associated with volumetric mammographic density
Authors: Brand, J.S
Humphreys, K
Li, J 
Karlsson, R
Hall, P
Czene, K
Keywords: adult
age
Article
body mass
breast cancer
breast density
cohort analysis
controlled study
female
gene locus
genetic association
genetic variability
genotype environment interaction
HABP2 gene
heterozygosity
human
INHBB gene
LINC01483 gene
linear regression analysis
major clinical study
mammography
menopause
oncogene
phenotype
principal component analysis
quantitative trait locus
single nucleotide polymorphism
aged
breast
breast density
breast tumor
diagnostic imaging
dna mutational analysis
genetic association study
genetic predisposition
genetics
middle aged
pathology
estrogen receptor alpha
HABP2 protein, human
INHBB protein, human
inhibin
serine proteinase
Adult
Aged
Breast
Breast Density
Breast Neoplasms
DNA Mutational Analysis
Estrogen Receptor alpha
Female
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Inhibin-beta Subunits
Mammography
Middle Aged
Polymorphism, Single Nucleotide
Serine Endopeptidases
Issue Date: 2018
Publisher: BMC
Citation: Brand, J.S, Humphreys, K, Li, J, Karlsson, R, Hall, P, Czene, K (2018). Common genetic variation and novel loci associated with volumetric mammographic density. Breast Cancer Research 20 (1) : 30. ScholarBank@NUS Repository. https://doi.org/10.1186/s13058-018-0954-6
Rights: Attribution 4.0 International
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 [h 2 SNP ]) 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). h 2 SNP (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 h 2 SNP to previously observed narrow-sense h 2 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 h 2 SNP /h 2 ratios varying between dense and nondense MD components. © 2018 The Author(s).
Source Title: Breast Cancer Research
URI: https://scholarbank.nus.edu.sg/handle/10635/183850
ISSN: 1465-5411
DOI: 10.1186/s13058-018-0954-6
Rights: Attribution 4.0 International
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