Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci.
Endometriosis is a chronic inflammatory condition in women that results in pelvic pain and subfertility, and has been associated with decreased body mass index (BMI). Genetic variants contributing to the heritable component have started to emerge from genome-wide association studies (GWAS), although...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2014
|
| _version_ | 1826267306671472640 |
|---|---|
| author | Rahmioglu, N Macgregor, S Drong, A Hedman, A Harris, H Randall, J Prokopenko, I Nyholt, DR Morris, A Montgomery, G Missmer, SA Lindgren, C Zondervan, K |
| author_facet | Rahmioglu, N Macgregor, S Drong, A Hedman, A Harris, H Randall, J Prokopenko, I Nyholt, DR Morris, A Montgomery, G Missmer, SA Lindgren, C Zondervan, K |
| author_sort | Rahmioglu, N |
| collection | OXFORD |
| description | Endometriosis is a chronic inflammatory condition in women that results in pelvic pain and subfertility, and has been associated with decreased body mass index (BMI). Genetic variants contributing to the heritable component have started to emerge from genome-wide association studies (GWAS), although the majority remain unknown. Unexpectedly, we observed an intergenic locus on 7p15.2 that was genome-wide significantly associated with both endometriosis and fat distribution (waist-to-hip ratio adjusted for BMI; WHRadjBMI) in an independent meta-GWAS of European ancestry individuals. This led us to investigate the potential overlap in genetic variants underlying the aetiology of endometriosis, WHRadjBMI and BMI using GWAS data. Our analyses demonstrated significant enrichment of common variants between fat distribution and endometriosis (P = 3.7 × 10(-3)), which was stronger when we restricted the investigation to more severe (Stage B) cases (P = 4.5 × 10(-4)). However, no genetic enrichment was observed between endometriosis and BMI (P = 0.79). In addition to 7p15.2, we identify four more variants with statistically significant evidence of involvement in both endometriosis and WHRadjBMI (in/near KIFAP3, CAB39L, WNT4, GRB14); two of these, KIFAP3 and CAB39L, are novel associations for both traits. KIFAP3, WNT4 and 7p15.2 are associated with the WNT signalling pathway; formal pathway analysis confirmed a statistically significant (P = 6.41 × 10(-4)) overrepresentation of shared associations in developmental processes/WNT signalling between the two traits. Our results demonstrate an example of potential biological pleiotropy that was hitherto unknown, and represent an opportunity for functional follow-up of loci and further cross-phenotype comparisons to assess how fat distribution and endometriosis pathogenesis research fields can inform each other. |
| first_indexed | 2024-03-06T20:52:10Z |
| format | Journal article |
| id | oxford-uuid:37f64e10-1eda-45f4-ba80-b823fc45f6f4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:52:10Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:37f64e10-1eda-45f4-ba80-b823fc45f6f42022-03-26T13:47:12ZGenome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:37f64e10-1eda-45f4-ba80-b823fc45f6f4EnglishSymplectic Elements at Oxford2014Rahmioglu, NMacgregor, SDrong, AHedman, AHarris, HRandall, JProkopenko, INyholt, DRMorris, AMontgomery, GMissmer, SALindgren, CZondervan, KEndometriosis is a chronic inflammatory condition in women that results in pelvic pain and subfertility, and has been associated with decreased body mass index (BMI). Genetic variants contributing to the heritable component have started to emerge from genome-wide association studies (GWAS), although the majority remain unknown. Unexpectedly, we observed an intergenic locus on 7p15.2 that was genome-wide significantly associated with both endometriosis and fat distribution (waist-to-hip ratio adjusted for BMI; WHRadjBMI) in an independent meta-GWAS of European ancestry individuals. This led us to investigate the potential overlap in genetic variants underlying the aetiology of endometriosis, WHRadjBMI and BMI using GWAS data. Our analyses demonstrated significant enrichment of common variants between fat distribution and endometriosis (P = 3.7 × 10(-3)), which was stronger when we restricted the investigation to more severe (Stage B) cases (P = 4.5 × 10(-4)). However, no genetic enrichment was observed between endometriosis and BMI (P = 0.79). In addition to 7p15.2, we identify four more variants with statistically significant evidence of involvement in both endometriosis and WHRadjBMI (in/near KIFAP3, CAB39L, WNT4, GRB14); two of these, KIFAP3 and CAB39L, are novel associations for both traits. KIFAP3, WNT4 and 7p15.2 are associated with the WNT signalling pathway; formal pathway analysis confirmed a statistically significant (P = 6.41 × 10(-4)) overrepresentation of shared associations in developmental processes/WNT signalling between the two traits. Our results demonstrate an example of potential biological pleiotropy that was hitherto unknown, and represent an opportunity for functional follow-up of loci and further cross-phenotype comparisons to assess how fat distribution and endometriosis pathogenesis research fields can inform each other. |
| spellingShingle | Rahmioglu, N Macgregor, S Drong, A Hedman, A Harris, H Randall, J Prokopenko, I Nyholt, DR Morris, A Montgomery, G Missmer, SA Lindgren, C Zondervan, K Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci. |
| title | Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci. |
| title_full | Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci. |
| title_fullStr | Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci. |
| title_full_unstemmed | Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci. |
| title_short | Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci. |
| title_sort | genome wide enrichment analysis between endometriosis and obesity related traits reveals novel susceptibility loci |
| work_keys_str_mv | AT rahmioglun genomewideenrichmentanalysisbetweenendometriosisandobesityrelatedtraitsrevealsnovelsusceptibilityloci AT macgregors genomewideenrichmentanalysisbetweenendometriosisandobesityrelatedtraitsrevealsnovelsusceptibilityloci AT dronga genomewideenrichmentanalysisbetweenendometriosisandobesityrelatedtraitsrevealsnovelsusceptibilityloci AT hedmana genomewideenrichmentanalysisbetweenendometriosisandobesityrelatedtraitsrevealsnovelsusceptibilityloci AT harrish genomewideenrichmentanalysisbetweenendometriosisandobesityrelatedtraitsrevealsnovelsusceptibilityloci AT randallj genomewideenrichmentanalysisbetweenendometriosisandobesityrelatedtraitsrevealsnovelsusceptibilityloci AT prokopenkoi genomewideenrichmentanalysisbetweenendometriosisandobesityrelatedtraitsrevealsnovelsusceptibilityloci AT nyholtdr genomewideenrichmentanalysisbetweenendometriosisandobesityrelatedtraitsrevealsnovelsusceptibilityloci AT morrisa genomewideenrichmentanalysisbetweenendometriosisandobesityrelatedtraitsrevealsnovelsusceptibilityloci AT montgomeryg genomewideenrichmentanalysisbetweenendometriosisandobesityrelatedtraitsrevealsnovelsusceptibilityloci AT missmersa genomewideenrichmentanalysisbetweenendometriosisandobesityrelatedtraitsrevealsnovelsusceptibilityloci AT lindgrenc genomewideenrichmentanalysisbetweenendometriosisandobesityrelatedtraitsrevealsnovelsusceptibilityloci AT zondervank genomewideenrichmentanalysisbetweenendometriosisandobesityrelatedtraitsrevealsnovelsusceptibilityloci |