Forest plots of the most significant <i>ATR</i> and <i>CHEK1</i> SNP associations.

<p>(A) the <i>ATR</i> rs6805118 associations. SEARCH: Studies of Epidemiology and Risk Factors in Cancer Heredity [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0068578#B8" target="_blank">8</a>]; NHS II: Nurses’ Health Study (premenopausal women) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0068578#B9" target="_blank">9</a>]; SBCS: Sheffield Breast Cancer Study (B) the <i>CHEK1</i> rs2155388 associations. UBCS: Utah Breast Cancer Study. For each panel, fixed effect estimate (pooled OR) is shown, with p value for homogeneity (the Cochran’s Q test, p_het) and I-squared for the amount of heterogeneity in parenthesis. DL pooled OR stands for the random effect model derived from the DerSimonian-Laird estimator.</p

Association plots of the 32 typed SNPs and 454 imputed variants in the <i>ATR</i> region.

<p>The most significant signal (rs6805118, p=7.6x10^-5) is labelled with the large blue circle. Circle symbols stand for the typed SNPs and diamond symbols represent the imputed variants. LD associations (r²) with rs6805118 were calculated in 85 CEU and 89 GBR (integrated call release as of 2010-11-23) in the 1000 genomes project. Gene transcripts are indicated by the dark green lines, with right arrowhead for the “+” strand and left arrowhead for the “-” strand. Recombination rate (blue line) was obtained from HapMap II.</p

Meta-analysis of the association of rs1802904 (<i>ATR</i> region) with breast cancer risk.

<p>Fixed effect estimate (pooled OR) is shown, with p value for homogeneity (the Cochran’s Q test, p_het) and I-squared for the amount of heterogeneity in parenthesis. DL pooled OR stands for the random effect model derived from the DerSimonian-Laird estimator. MEC: Multiethnic Cohort Study [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0068578#B7" target="_blank">7</a>]; SEARCH: Studies of Epidemiology and Risk Factors in Cancer Heredity [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0068578#B8" target="_blank">8</a>]; NHS II: Nurses’ Health Study (postmenopausal women) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0068578#B22" target="_blank">22</a>]; SBCS: Sheffield Breast Cancer Study.</p

Association plots of the 44 typed SNPs and 434 imputed variants in the <i>CHEK1</i> region.

<p>The most significant signal (rs2155388, p=3.1x10^-5) is labelled with the large blue circle. The typed SNPs and the imputed variants are shown in the circle and diamond symbols, respectively. Pair-wise r² with rs2155388 were calculated in 85 CEU and 89 GBR (integrated call release as of 2010-11-23) in the 1000 genomes project. Gene transcripts are indicated by the dark green lines, with right arrowhead for the “+” strand and left arrowhead for the “-” strand. Recombination rate (blue line) was obtained from HapMap II.</p

Association of rs2046210 and rs12662670 with breast cancer.

<p>Results are presented overall and separately for Europeans and Asians. Pooled analyses adjusted for study only as well as adjusted for rs12662670 or rs2046210, respectively, in addition to study were performed.</p>a<p>P-value derived from the log-additive model.</p>b<p>Odds ratio per minor allele (A allele for rs2046210, G allele for rs12662670).</p>c<p>Odds ratio relative to the major allele homozygous (GT) genotype.</p

Association of rs2046210 with breast cancer in Asian ER

<p>−<b>*versus ER+**cases and controls.</b> *Estrogen receptor negative; **Estrogen receptor positive.</p

Association of rs12662670 with breast cancer in European ER

<p>−<b>*versus ER+**cases and controls.</b> *Estrogen receptor negative; **Estrogen receptor positive.</p

Linkage disequilibrium blocks in the <i>ESR1</i> region.

<p>Five SNPs tagged (at r2>0.9) by rs12662670 and three by rs2046210 are marked by arrows (dark and light grey respectively); rs12662670 and rs2046210 are marked by stars; rs3757318 and rs9397435 are marked by points; blocks were generated using data from the 1000 Genomes Project and HapMap; blocks include all single nucleotide polymorphisms with a minor allele frequency >0.05. The directions of translation of <i>ESR1</i> and <i>C6orf97</i> are marked and other genes in the locus are listed.</p

Association of haplotypes composed of rs2046210 and rs12662670 with breast cancer.

<p>Results are presented overall and separately for Europeans and Asians. Pooled analyses adjusted for study were performed.</p>a<p>Odds ratio per haplotype compared to the reference haplotype (i.e., the most frequent haplotype).</p>b<p>P-value derived from the log-additive model.</p>c<p>Minor allele.</p>d<p>Reference haplotype.</p

Association of rs2046210 and rs12662670 with risk of ER−^*/ER+^** breast cancer.

<p>Results are presented overall as well as separately for Europeans and Asians. Pooled analyses adjusted for the studies were performed. A log-additive genetic model was assumed.</p>*<p>Estrogen receptor negative.</p>**<p>Estrogen receptor positive.</p>a<p>Odds ratio per minor allele (A allele for rs2046210, G allele for rs12662670) derived from case-control logistic regression restricted to ER+ or ER− cases, respectively, and the whole control sample.</p>b<p>P-value derived from the log-additive model derived from case-control logistic regression restricted to ER+ or ER− cases, respectively, and the whole control sample.</p>c<p>P-value for heterogeneity between estimates of genetic main effects derived from case-only analysis.</p