The Contribution of Rare Variation to Prostate Cancer Heritability  

Oleh:

Mancuso, Nicholas ; Rohland, Nadin ; Rand, Kristin A. ; Tandon, Arti ; Allen, Alexander ; Quinque, Dominique ; Mallick, Swapan ; Heng Li ; Stram, Alex ; Xin Sheng ; Kote-Jarai, Zsofia ; Easton, Douglas F. ; Eeles, Rosalind A. ; Le Marchand, Loic ; Lubwama, Alex ; Stram, Daniel ; Watya, Stephen ; Conti, David V. ; Henderson, Brian ; Haiman, Christopher A. ; Pasaniuc, Bogdan ; Reich, David

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Nature Genetics vol. 48 no. 01 (Jan. 2016), page 30-35.
Topik: DNA Sequencing; Genetic Association Study; Prostate Cancer

Ketersediaan

Perpustakaan FK Nomor Panggil: N12.K Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

Lihat Detail Induk

Isi artikel

We report targeted sequencing of 63 known prostate cancer risk regions in a multi-ancestry study of 9,237 men and use the data to explore the contribution of low-frequency variation to disease risk. We show that SNPs with minor allele frequencies (MAFs) of 0.1–1% explain a substantial fraction of prostate cancer risk in men of African ancestry. We estimate that these SNPs account for 0.12 (standard error (s.e.) = 0.05) of variance in risk (~42% of the variance contributed by SNPs with MAF of 0.1–50%). This contribution is much larger than the fraction of neutral variation due to SNPs in this class, implying that natural selection has driven down the frequency of many prostate cancer risk alleles; we estimate the coupling between selection and allelic effects at 0.48 (95% confidence interval [0.19, 0.78]) under the Eyre-Walker model. Our results indicate that rare variants make a disproportionate contribution to genetic risk for prostate cancer and suggest the possibility that rare variants may also have an outsize effect on other common traits.

Opini Anda

Klik untuk menuliskan opini Anda tentang koleksi ini!

Kembali