Genetic relationship between endometriosis and melanoma

Fei Yang; Sally Mortlock; Stuart MacGregor; Mark M. Iles; Maria Teresa Landi; Jianxin Shi; Matthew H. Law; Grant W. Montgomery; The International Endometriosis Genetics Consortium

doi:10.3389/frph.2021.711123

Genetic relationship between endometriosis and melanoma

Fei Yang, Sally Mortlock^*, Stuart MacGregor, Mark M. Iles, Maria Teresa Landi, Jianxin Shi, Matthew H. Law, Grant W. Montgomery, The International Endometriosis Genetics Consortium

^*Corresponding author for this work

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Abstract

Epidemiological studies have observed that risk of endometriosis is associated with history of cutaneous melanoma and vice versa. Evidence for shared biological mechanisms between the two traits is limited. The aim of this study was to investigate the genetic correlation and causal relationship between endometriosis and melanoma. Summary statistics from genome-wide association meta-analyses (GWAS) for endometriosis and melanoma were used to estimate the genetic correlation between the traits and Mendelian randomization was used to test for a causal association. When using summary statistics from separate female and male melanoma cohorts we identified a significant positive genetic correlation between melanoma in females and endometriosis (r_g = 0.144, se = 0.065, p = 0.025). However, we find no evidence of a correlation between endometriosis and melanoma in males or a combined melanoma dataset. Endometriosis was not genetically correlated with skin color, red hair, childhood sunburn occasions, ease of skin tanning, or nevus count suggesting that the correlation between endometriosis and melanoma in females is unlikely to be influenced by pigmentary traits. Mendelian Randomization analyses also provided evidence for a relationship between the genetic risk of melanoma in females and endometriosis. Colocalization analysis identified 27 genomic loci jointly associated with the two diseases regions that contain different causal variants influencing each trait independently. This study provides evidence of a small genetic correlation and relationship between the genetic risk of melanoma in females and endometriosis. Genetic risk does not equate to disease occurrence and differences in the pathogenesis and age of onset of both diseases means it is unlikely that occurrence of melanoma causes endometriosis. This study instead provides evidence that having an increased genetic risk for melanoma in females is related to increased risk of endometriosis. Larger GWAS studies with increased power will be required to further investigate these associations.

Original language	English
Article number	711123
Pages (from-to)	1-10
Number of pages	10
Journal	Frontiers in Reproductive Health
Volume	3
DOIs	https://doi.org/10.3389/frph.2021.711123
Publication status	Published - 2 Aug 2021
Externally published	Yes

Bibliographical note

Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

endometriosis
genetic correlation
genetic risk
melanoma
mendelian randomization

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10.3389/frph.2021.711123Licence: CC BY

Publisher version (open access)Final published version, 739 KBLicence: CC BY

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title = "Genetic relationship between endometriosis and melanoma",

abstract = "Epidemiological studies have observed that risk of endometriosis is associated with history of cutaneous melanoma and vice versa. Evidence for shared biological mechanisms between the two traits is limited. The aim of this study was to investigate the genetic correlation and causal relationship between endometriosis and melanoma. Summary statistics from genome-wide association meta-analyses (GWAS) for endometriosis and melanoma were used to estimate the genetic correlation between the traits and Mendelian randomization was used to test for a causal association. When using summary statistics from separate female and male melanoma cohorts we identified a significant positive genetic correlation between melanoma in females and endometriosis (rg = 0.144, se = 0.065, p = 0.025). However, we find no evidence of a correlation between endometriosis and melanoma in males or a combined melanoma dataset. Endometriosis was not genetically correlated with skin color, red hair, childhood sunburn occasions, ease of skin tanning, or nevus count suggesting that the correlation between endometriosis and melanoma in females is unlikely to be influenced by pigmentary traits. Mendelian Randomization analyses also provided evidence for a relationship between the genetic risk of melanoma in females and endometriosis. Colocalization analysis identified 27 genomic loci jointly associated with the two diseases regions that contain different causal variants influencing each trait independently. This study provides evidence of a small genetic correlation and relationship between the genetic risk of melanoma in females and endometriosis. Genetic risk does not equate to disease occurrence and differences in the pathogenesis and age of onset of both diseases means it is unlikely that occurrence of melanoma causes endometriosis. This study instead provides evidence that having an increased genetic risk for melanoma in females is related to increased risk of endometriosis. Larger GWAS studies with increased power will be required to further investigate these associations.",

keywords = "endometriosis, genetic correlation, genetic risk, melanoma, mendelian randomization",

author = "Fei Yang and Sally Mortlock and Stuart MacGregor and Iles, {Mark M.} and Landi, {Maria Teresa} and Jianxin Shi and Law, {Matthew H.} and Montgomery, {Grant W.} and {The International Endometriosis Genetics Consortium}",

note = "Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2021",

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doi = "10.3389/frph.2021.711123",

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T1 - Genetic relationship between endometriosis and melanoma

AU - Yang, Fei

AU - Mortlock, Sally

AU - MacGregor, Stuart

AU - Iles, Mark M.

AU - Landi, Maria Teresa

AU - Shi, Jianxin

AU - Law, Matthew H.

AU - Montgomery, Grant W.

AU - The International Endometriosis Genetics Consortium

N1 - Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2021/8/2

Y1 - 2021/8/2

N2 - Epidemiological studies have observed that risk of endometriosis is associated with history of cutaneous melanoma and vice versa. Evidence for shared biological mechanisms between the two traits is limited. The aim of this study was to investigate the genetic correlation and causal relationship between endometriosis and melanoma. Summary statistics from genome-wide association meta-analyses (GWAS) for endometriosis and melanoma were used to estimate the genetic correlation between the traits and Mendelian randomization was used to test for a causal association. When using summary statistics from separate female and male melanoma cohorts we identified a significant positive genetic correlation between melanoma in females and endometriosis (rg = 0.144, se = 0.065, p = 0.025). However, we find no evidence of a correlation between endometriosis and melanoma in males or a combined melanoma dataset. Endometriosis was not genetically correlated with skin color, red hair, childhood sunburn occasions, ease of skin tanning, or nevus count suggesting that the correlation between endometriosis and melanoma in females is unlikely to be influenced by pigmentary traits. Mendelian Randomization analyses also provided evidence for a relationship between the genetic risk of melanoma in females and endometriosis. Colocalization analysis identified 27 genomic loci jointly associated with the two diseases regions that contain different causal variants influencing each trait independently. This study provides evidence of a small genetic correlation and relationship between the genetic risk of melanoma in females and endometriosis. Genetic risk does not equate to disease occurrence and differences in the pathogenesis and age of onset of both diseases means it is unlikely that occurrence of melanoma causes endometriosis. This study instead provides evidence that having an increased genetic risk for melanoma in females is related to increased risk of endometriosis. Larger GWAS studies with increased power will be required to further investigate these associations.

AB - Epidemiological studies have observed that risk of endometriosis is associated with history of cutaneous melanoma and vice versa. Evidence for shared biological mechanisms between the two traits is limited. The aim of this study was to investigate the genetic correlation and causal relationship between endometriosis and melanoma. Summary statistics from genome-wide association meta-analyses (GWAS) for endometriosis and melanoma were used to estimate the genetic correlation between the traits and Mendelian randomization was used to test for a causal association. When using summary statistics from separate female and male melanoma cohorts we identified a significant positive genetic correlation between melanoma in females and endometriosis (rg = 0.144, se = 0.065, p = 0.025). However, we find no evidence of a correlation between endometriosis and melanoma in males or a combined melanoma dataset. Endometriosis was not genetically correlated with skin color, red hair, childhood sunburn occasions, ease of skin tanning, or nevus count suggesting that the correlation between endometriosis and melanoma in females is unlikely to be influenced by pigmentary traits. Mendelian Randomization analyses also provided evidence for a relationship between the genetic risk of melanoma in females and endometriosis. Colocalization analysis identified 27 genomic loci jointly associated with the two diseases regions that contain different causal variants influencing each trait independently. This study provides evidence of a small genetic correlation and relationship between the genetic risk of melanoma in females and endometriosis. Genetic risk does not equate to disease occurrence and differences in the pathogenesis and age of onset of both diseases means it is unlikely that occurrence of melanoma causes endometriosis. This study instead provides evidence that having an increased genetic risk for melanoma in females is related to increased risk of endometriosis. Larger GWAS studies with increased power will be required to further investigate these associations.

KW - endometriosis

KW - genetic correlation

KW - genetic risk

KW - melanoma

KW - mendelian randomization

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U2 - 10.3389/frph.2021.711123

DO - 10.3389/frph.2021.711123

M3 - Article

C2 - 36304021

SN - 2673-3153

VL - 3

SP - 1

EP - 10

JO - Frontiers in Reproductive Health

JF - Frontiers in Reproductive Health

M1 - 711123

ER -

Genetic relationship between endometriosis and melanoma

Abstract

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Keywords

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