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Fine mapping of the uterine leiomyoma locus on 1q43 close to a lncRNA in the RGS7-FH interval.

Aissani B, Zhang K, Mensenkamp AR, Menko FH, Wiener HW - Endocr. Relat. Cancer (2015)

Bottom Line: In race-combined analyses and in meta-analyses (n=916), we identified promising associations with risk peaking upstream of a non-protein coding RNA (lncRNA) locus located in the RGS7-FH interval closer to RGS7, and associations with tumor size peaking in the distal phospholipase D family, member 5 (PLD5) gene at rs2654879 (P=1.7×10(-4)).We corroborated previously reported FH mutations in nine out of the 18 HLRCC-associated UL cases and identified two missense mutations in FH in only two nonsyndromic UL cases and one control.While the identified variations at 1q43 represent a potential risk locus for UL, future replication analyses are required to substantiate our observation.

View Article: PubMed Central - PubMed

Affiliation: Department of EpidemiologyR217JDepartment of BiostatisticsSchool of Public Health, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, Alabama 35294-0022, USADepartment of Human GeneticsRadboud University Medical Center Nijmegen, Nijmegen, The NetherlandsNetherlands Cancer InstituteAmsterdam, The Netherlands baissani@uab.edu.

No MeSH data available.


Related in: MedlinePlus

Fine mapping of chromosome 1q43 variants associated with risk and size of uterine fibroids in the NIEHS uterine fibroid study. The plot shows the strength of association (expressed as minus log10 of P value) between 1780 quality control-filtered single nucleotide polymorphisms (SNPs) and uterine fibroid outcomes (filled diamonds: risk; empty circles: tumor size including controls as the category with the lowest level; empty triangles: tumor size in case-only design) obtained for a pooled sample (525 African American and 391 European American individuals) using logistic regression models with adjustments for covariates (age, age-at-menarche, parity, BMI and physical activity) and for SNP by race interaction term.
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fig1: Fine mapping of chromosome 1q43 variants associated with risk and size of uterine fibroids in the NIEHS uterine fibroid study. The plot shows the strength of association (expressed as minus log10 of P value) between 1780 quality control-filtered single nucleotide polymorphisms (SNPs) and uterine fibroid outcomes (filled diamonds: risk; empty circles: tumor size including controls as the category with the lowest level; empty triangles: tumor size in case-only design) obtained for a pooled sample (525 African American and 391 European American individuals) using logistic regression models with adjustments for covariates (age, age-at-menarche, parity, BMI and physical activity) and for SNP by race interaction term.

Mentions: To finely map the putative UL susceptibility locus on chromosome 1q43, we re-evaluated the association with the entire set of 1780 SNPs (1559 SNPs from the initial study (Aissani et al. 2013) that was performed only in race-stratified models and the 221 post-NGS SNPs) in analyses of pooled AA and EA samples and in meta-analyses. The small sample (n=70) representing the ethnic group defined as ‘other’ was excluded to allow the results of race-stratified and race-pooled designs to be compared. The results of the combined analysis (Fig. 1) and meta-analysis (Supplementary Figure S3, see section on supplementary data given at the end of this article) showed a prominent peak of association with risk centered in the intergenic interval delimited by centromeric RGS7 and telomeric FH genes. More precisely, the association with risk peaked at rs2341938 (P=1.6×10−4) in the combined analysis and at the nearby rs78220092 SNP (P=5.4×10−5) in meta-analysis (Table 2 and Supplementary Table S1). The negative association with rs78220092 in the pooled sample is most likely driven by the low allele frequency of rs78220092 in the EA group.


Fine mapping of the uterine leiomyoma locus on 1q43 close to a lncRNA in the RGS7-FH interval.

Aissani B, Zhang K, Mensenkamp AR, Menko FH, Wiener HW - Endocr. Relat. Cancer (2015)

Fine mapping of chromosome 1q43 variants associated with risk and size of uterine fibroids in the NIEHS uterine fibroid study. The plot shows the strength of association (expressed as minus log10 of P value) between 1780 quality control-filtered single nucleotide polymorphisms (SNPs) and uterine fibroid outcomes (filled diamonds: risk; empty circles: tumor size including controls as the category with the lowest level; empty triangles: tumor size in case-only design) obtained for a pooled sample (525 African American and 391 European American individuals) using logistic regression models with adjustments for covariates (age, age-at-menarche, parity, BMI and physical activity) and for SNP by race interaction term.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526794&req=5

fig1: Fine mapping of chromosome 1q43 variants associated with risk and size of uterine fibroids in the NIEHS uterine fibroid study. The plot shows the strength of association (expressed as minus log10 of P value) between 1780 quality control-filtered single nucleotide polymorphisms (SNPs) and uterine fibroid outcomes (filled diamonds: risk; empty circles: tumor size including controls as the category with the lowest level; empty triangles: tumor size in case-only design) obtained for a pooled sample (525 African American and 391 European American individuals) using logistic regression models with adjustments for covariates (age, age-at-menarche, parity, BMI and physical activity) and for SNP by race interaction term.
Mentions: To finely map the putative UL susceptibility locus on chromosome 1q43, we re-evaluated the association with the entire set of 1780 SNPs (1559 SNPs from the initial study (Aissani et al. 2013) that was performed only in race-stratified models and the 221 post-NGS SNPs) in analyses of pooled AA and EA samples and in meta-analyses. The small sample (n=70) representing the ethnic group defined as ‘other’ was excluded to allow the results of race-stratified and race-pooled designs to be compared. The results of the combined analysis (Fig. 1) and meta-analysis (Supplementary Figure S3, see section on supplementary data given at the end of this article) showed a prominent peak of association with risk centered in the intergenic interval delimited by centromeric RGS7 and telomeric FH genes. More precisely, the association with risk peaked at rs2341938 (P=1.6×10−4) in the combined analysis and at the nearby rs78220092 SNP (P=5.4×10−5) in meta-analysis (Table 2 and Supplementary Table S1). The negative association with rs78220092 in the pooled sample is most likely driven by the low allele frequency of rs78220092 in the EA group.

Bottom Line: In race-combined analyses and in meta-analyses (n=916), we identified promising associations with risk peaking upstream of a non-protein coding RNA (lncRNA) locus located in the RGS7-FH interval closer to RGS7, and associations with tumor size peaking in the distal phospholipase D family, member 5 (PLD5) gene at rs2654879 (P=1.7×10(-4)).We corroborated previously reported FH mutations in nine out of the 18 HLRCC-associated UL cases and identified two missense mutations in FH in only two nonsyndromic UL cases and one control.While the identified variations at 1q43 represent a potential risk locus for UL, future replication analyses are required to substantiate our observation.

View Article: PubMed Central - PubMed

Affiliation: Department of EpidemiologyR217JDepartment of BiostatisticsSchool of Public Health, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, Alabama 35294-0022, USADepartment of Human GeneticsRadboud University Medical Center Nijmegen, Nijmegen, The NetherlandsNetherlands Cancer InstituteAmsterdam, The Netherlands baissani@uab.edu.

No MeSH data available.


Related in: MedlinePlus