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Y chromosome mosaicism is associated with age-related macular degeneration

Y chromosome mosaicism is associated with age-related macular degeneration
Y chromosome mosaicism is associated with age-related macular degeneration
Age-related macular degeneration (AMD) is the leading cause of blindness in industrialized countries and thereby a major individual but also a socio-economic burden. Y chromosome loss in nucleated blood cells has been implicated in age-related diseases such as Alzheimer disease and was shown to be caused by increasing age, smoking and genetic factors. Mosaic loss of Y chromosome (mLOY) in peripheral blood was estimated from normalized dosages of genotyping chip data covering the male-specific region of the Y chromosome. After quality control, we assessed the association of mLOY on AMD risk in 5,772 male cases and 6,732 male controls. In controls the prevalence of mLOY increased significantly with age which is consistent with previous reports. Importantly, mLOY was associated with late stage AMD with genome-wide significance (OR: 1.332 [95% CI: 1.206; 1.472], P=1.60e-08), independent of age, the AMD genetic risk score and the first two principle components of ancestry. Additionally conditioning on smoking behaviour had no influence on the observed association strength. mLOY was strongest associated in individuals aged between 65 and 75 years. Taken together, mLOY is significantly associated with risk for AMD, independent of known and potential confounding factors.
Y chromosome; mosaicism; chromosomal loss; age-related macular degeneration; mLOY; smoking
1018-4813
Grassmann, Felix
a72edc86-c7e0-495f-a827-51d7db514076
Kiel, Christina
50c548c1-dd43-442f-93cd-ccad140490e9
den Hollander, Anneke I.
55961992-9080-4986-ae08-f3e680a49b11
Weeks, Daniel E.
f98f5f10-5aa6-4258-8fd4-3fe60937af5d
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Cipriani, Valentina
df4a538c-6639-45c5-818a-255aa59b44cf
Weber, Bernhard H.F.
2d73f4e5-de30-4807-8926-c8f6c1288840
Grassmann, Felix
a72edc86-c7e0-495f-a827-51d7db514076
Kiel, Christina
50c548c1-dd43-442f-93cd-ccad140490e9
den Hollander, Anneke I.
55961992-9080-4986-ae08-f3e680a49b11
Weeks, Daniel E.
f98f5f10-5aa6-4258-8fd4-3fe60937af5d
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Cipriani, Valentina
df4a538c-6639-45c5-818a-255aa59b44cf
Weber, Bernhard H.F.
2d73f4e5-de30-4807-8926-c8f6c1288840

Grassmann, Felix, Kiel, Christina, den Hollander, Anneke I., Weeks, Daniel E., Lotery, Andrew, Cipriani, Valentina and Weber, Bernhard H.F. (2018) Y chromosome mosaicism is associated with age-related macular degeneration. European Journal of Human Genetics, [249-18-EJHGR]. (doi:10.1038/s41431-018-0238-8).

Record type: Article

Abstract

Age-related macular degeneration (AMD) is the leading cause of blindness in industrialized countries and thereby a major individual but also a socio-economic burden. Y chromosome loss in nucleated blood cells has been implicated in age-related diseases such as Alzheimer disease and was shown to be caused by increasing age, smoking and genetic factors. Mosaic loss of Y chromosome (mLOY) in peripheral blood was estimated from normalized dosages of genotyping chip data covering the male-specific region of the Y chromosome. After quality control, we assessed the association of mLOY on AMD risk in 5,772 male cases and 6,732 male controls. In controls the prevalence of mLOY increased significantly with age which is consistent with previous reports. Importantly, mLOY was associated with late stage AMD with genome-wide significance (OR: 1.332 [95% CI: 1.206; 1.472], P=1.60e-08), independent of age, the AMD genetic risk score and the first two principle components of ancestry. Additionally conditioning on smoking behaviour had no influence on the observed association strength. mLOY was strongest associated in individuals aged between 65 and 75 years. Taken together, mLOY is significantly associated with risk for AMD, independent of known and potential confounding factors.

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Accepted/In Press date: 18 July 2018
e-pub ahead of print date: 29 August 2018
Keywords: Y chromosome; mosaicism; chromosomal loss; age-related macular degeneration; mLOY; smoking

Identifiers

Local EPrints ID: 422701
URI: http://eprints.soton.ac.uk/id/eprint/422701
ISSN: 1018-4813
PURE UUID: aea54ee7-42f5-45eb-9bbc-f9fc85bde23a
ORCID for Andrew Lotery: ORCID iD orcid.org/0000-0001-5541-4305

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Date deposited: 31 Jul 2018 16:30
Last modified: 26 Nov 2021 07:09

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Contributors

Author: Felix Grassmann
Author: Christina Kiel
Author: Anneke I. den Hollander
Author: Daniel E. Weeks
Author: Andrew Lotery ORCID iD
Author: Valentina Cipriani
Author: Bernhard H.F. Weber

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