Grassmann, F;
Kiel, C;
Zimmermann, ME;
Gorski, M;
Grassmann, V;
Stark, K;
Heid, IM;
(2017)
Genetic pleiotropy between age-related macular degeneration and 16 complex diseases and traits.
Genome Medicine
, 9
, Article 29. 10.1186/s13073-017-0418-0.
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Abstract
BACKGROUND: Age-related macular degeneration (AMD) is a common condition of vision loss with disease development strongly influenced by environmental and genetic factors. Recently, 34 loci were associated with AMD at genome-wide significance. So far, little is known about a genetic overlap between AMD and other complex diseases or disease-relevant traits. METHODS: For each of 60 complex diseases/traits with publicly available genome-wide significant association data, the lead genetic variant per independent locus was extracted and a genetic score was calculated for each disease/trait as the weighted sum of risk alleles. The association with AMD was estimated based on 16,144 AMD cases and 17,832 controls using logistic regression. RESULTS: Of the respective disease/trait variance, the 60 genetic scores explained on average 4.8% (0.27–20.69%) and 16 of them were found to be significantly associated with AMD (Q-values < 0.01, p values from < 1.0 × 10–16 to 1.9 × 10–3). Notably, an increased risk for AMD was associated with reduced risk for cardiovascular diseases, increased risk for autoimmune diseases, higher HDL and lower LDL levels in serum, lower bone-mineral density as well as an increased risk for skin cancer. By restricting the analysis to 1824 variants initially used to compute the 60 genetic scores, we identified 28 novel AMD risk variants (Q-values < 0.01, p values from 1.1 × 10–7 to 3.0 × 10–4), known to be involved in cardiovascular disorders, lipid metabolism, autoimmune diseases, anthropomorphic traits, ocular disorders, and neurological diseases. The latter variants represent 20 novel AMD-associated, pleiotropic loci. Genes in the novel loci reinforce previous findings strongly implicating the complement system in AMD pathogenesis. CONCLUSIONS: We demonstrate a substantial overlap of the genetics of several complex diseases/traits with AMD and provide statistically significant evidence for an additional 20 loci associated with AMD. This highlights the possibility that so far unrelated pathologies may have disease pathways in common.
| Type: | Article |
|---|---|
| Title: | Genetic pleiotropy between age-related macular degeneration and 16 complex diseases and traits |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s13073-017-0418-0 |
| Publisher version: | https://doi.org/10.1186/s13073-017-0418-0 |
| Language: | English |
| Additional information: | This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, Age-Related Macular Degeneration, AMD, Genetic Risk Scores, GRS, Genetic Association Studies, Complex Traits, Shared Genetics, Genome-Wide Association, Prostate-Cancer Susceptibility, Chronic Kidney-Disease, Open-Angle Glaucoma, Rheumatoid-Arthritis, Risk Loci, Japanese Population, Multiple Loci, Cardiovascular-Disease, Melanoma Risk |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10054235 |
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