NDLI: Endometriosis Is Associated with Rare Copy Number Variants

Content Provider	PubMed Central
Author	Rakesh, Chettier Ward, Kenneth Albertsen, Hans M.
Editor	Scott, Rodney John
Copyright Year	2014
Abstract	Endometriosis is a complex gynecological condition that affects 6–10% of women in their reproductive years and is defined by the presence of endometrial glands and stroma outside the uterus. Twin, family, and genome-wide association (GWA) studies have confirmed a genetic role, yet only a small part of the genetic risk can be explained by SNP variation. Copy number variants (CNVs) account for a greater portion of human genetic variation than SNPs and include more recent mutations of large effect. CNVs, likely to be prominent in conditions with decreased reproductive fitness, have not previously been examined as a genetic contributor to endometriosis. Here we employ a high-density genotyping microarray in a genome-wide survey of CNVs in a case-control population that includes 2,126 surgically confirmed endometriosis cases and 17,974 population controls of European ancestry. We apply stringent quality filters to reduce the false positive rate common to many CNV-detection algorithms from 77.7% to 7.3% without noticeable reduction in the true positive rate. We detected no differences in the CNV landscape between cases and controls on the global level which showed an average of 1.92 CNVs per individual with an average size of 142.3 kb. On the local level we identify 22 CNV-regions at the nominal significance threshold (P<0.05), which is greater than the 8.15 CNV-regions expected based on permutation analysis (P<0.001). Three CNV's passed a genome-wide P-value threshold of 9.3×10−4; a deletion at SGCZ on 8p22 (P = 7.3×10−4, OR = 8.5, Cl = 2.3–31.7), a deletion in MALRD1 on 10p12.31 (P = 5.6×10−4, OR = 14.1, Cl = 2.7–90.9), and a deletion at 11q14.1 (P = 5.7×10−4, OR = 33.8, Cl = 3.3–1651). Two SNPs within the 22 CNVRs show significant genotypic association with endometriosis after adjusting for multiple testing; rs758316 in DPP6 on 7q36.2 (P = 0.0045) and rs4837864 in ASTN2 on 9q33.1 (P = 0.0002). Together, the CNV-loci are detected in 6.9% of affected women compared to 2.1% in the general population.
Related Links	http://dx.doi.org/10.1371/journal.pone.0103968
Starting Page	103968
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	8
Volume Number	9
Language	English
Publisher	Public Library of Science
Publisher Date	2014-08-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Somatic Copy Number Alterations Associated with Japanese or Endometriosis in Ovarian Clear Cell Adenocarcinoma

Mitochondrial DNA Copy Number Is Associated with Breast Cancer Risk

Copy Number Variants in German Patients with Schizophrenia

Identification of De Novo Copy Number Variants Associated with Human Disorders of Sexual Development

Rare Copy Number Variants Identified Suggest the Regulating Pathways in Hypertension-Related Left Ventricular Hypertrophy

Leukocyte Mitochondrial DNA Copy Number Is Associated with Chronic Obstructive Pulmonary Disease

Insights on the Functional Impact of MicroRNAs Present in Autism-Associated Copy Number Variants

Copy Number Variants in the Kallikrein Gene Cluster

Transgene Expression Is Associated with Copy Number and Cytomegalovirus Promoter Methylation in Transgenic Pigs

Endometriosis Is Associated with Rare Copy Number Variants

Similar Documents

Somatic Copy Number Alterations Associated with Japanese or Endometriosis in Ovarian Clear Cell Adenocarcinoma

Mitochondrial DNA Copy Number Is Associated with Breast Cancer Risk

Copy Number Variants in German Patients with Schizophrenia

Identification of De Novo Copy Number Variants Associated with Human Disorders of Sexual Development

Rare Copy Number Variants Identified Suggest the Regulating Pathways in Hypertension-Related Left Ventricular Hypertrophy

Leukocyte Mitochondrial DNA Copy Number Is Associated with Chronic Obstructive Pulmonary Disease

Insights on the Functional Impact of MicroRNAs Present in Autism-Associated Copy Number Variants

Copy Number Variants in the Kallikrein Gene Cluster

Transgene Expression Is Associated with Copy Number and Cytomegalovirus Promoter Methylation in Transgenic Pigs

Endometriosis Is Associated with Rare Copy Number Variants