eprintid: 10058812
rev_number: 36
eprint_status: archive
userid: 608
dir: disk0/10/05/88/12
datestamp: 2018-10-19 11:59:56
lastmod: 2021-12-06 00:43:58
status_changed: 2018-10-19 11:59:56
type: article
metadata_visibility: show
creators_name: Colijn, JM
creators_name: Hollander, AID
creators_name: Demirkan, A
creators_name: Cougnard-Grégoire, A
creators_name: Verzijden, T
creators_name: Kersten, E
creators_name: Meester, MA
creators_name: Merle, BMJ
creators_name: Papageorgiou, G
creators_name: Ahmad, S
creators_name: Mulder, MT
creators_name: Costa, MA
creators_name: Benlian, P
creators_name: Bertelsen, G
creators_name: Bron, A
creators_name: Claes, B
creators_name: Creuzot-Garcher, C
creators_name: Erke, MG
creators_name: Fauser, S
creators_name: Foster, PJ
creators_name: Hammond, CJ
creators_name: Hense, HW
creators_name: Hoyng, CB
creators_name: Khawaja, AP
creators_name: Korobelnik, J
creators_name: Piermarocchi, S
creators_name: Segato, T
creators_name: Silva, R
creators_name: Souied, EH
creators_name: Williams, KM
creators_name: van Duijn, CM
creators_name: Delcourt, C
creators_name: Klaver, CCW
creators_name: E3 Consortium and EYE-RISK Consortium, .
title: Increased High Density Lipoprotein-levels associated with Age-related Macular degeneration. Evidence from the EYE-RISK and E3 Consortia
ispublished: pub
subjects: MOOR
divisions: UCL
divisions: B02
divisions: C07
divisions: D08
divisions: D12
divisions: G19
divisions: B04
divisions: C05
divisions: F42
keywords: Age-related macular degeneration, E3 Consortium, Running head: High HDL associated with AMD, cholesterol, high-density lipoproteins, lipids
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: PURPOSE: Genetic and epidemiologic studies have shown that lipid genes and High Density Lipoproteins (HDL) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relation to AMD in a large European dataset, and investigated whether this relationship is driven by certain sub fractions. DESIGN: (Pooled) analysis of cross-sectional data. PARTICIPANTS: 30,953 individuals aged 50+ participating in the E3 consortium; and 1530 individuals from the Rotterdam Study with lipid sub fraction data. METHODS: In E3, AMD features were graded per eye on fundus photographs using the Rotterdam Classification. Routine blood lipid measurements were available from each participant. Data on genetics, medication and confounders such as body mass index, were obtained from a common database. In a subgroup of the Rotterdam Study, lipid sub fractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random-effect were used to estimate the associations. MAIN OUTCOME MEASURES: early, late or any AMD, phenotypic features of early AMD, lipid measurements. RESULTS: HDL was associated with an increased risk of AMD, corrected for potential confounders (Odds Ratio (OR) 1.21 per 1mmol/L increase (95% confidence interval[CI] 1.14-1.29); while triglycerides were associated with a decreased risk (OR 0.94 per 1mmol/L increase [95%CI 0.91-0.97]). Both were associated with drusen size, higher HDL raises the odds of larger drusen while higher triglycerides decreases the odds. LDL-cholesterol only reached statistical significance in the association with early AMD (p=0.045). Regarding lipid sub fractions: the concentration of extra-large HDL particles showed the most prominent association with AMD (OR 1.24 [95%CI 1.10-1.40]). The CETP risk variant (rs17231506) for AMD was in line with increased-HDL levels (p=7.7x10-7); but LIPC risk variants (rs2043085, rs2070895) were associated in an opposite way (p=1.0x10-6 and 1.6x10-4). CONCLUSIONS: Our study suggests that HDL-cholesterol is associated with increased risk of AMD and triglycerides negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL sub fractions seem to be drivers in the relation with AMD, variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains a question to be answered.
date: 2019-03
date_type: published
official_url: https://doi.org/10.1016/j.ophtha.2018.09.045
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1593893
doi: 10.1016/j.ophtha.2018.09.045
pii: S0161-6420(18)31091-1
lyricists_name: Bhattacharya, Shom
lyricists_name: Bobak, Martin
lyricists_name: Foster, Paul
lyricists_name: Khawaja, Anthony
lyricists_name: Lengyel, Imre
lyricists_name: Luthert, Philip
lyricists_name: Williams, Katie
lyricists_id: SSBHA56
lyricists_id: MBOBA10
lyricists_id: PJFOS52
lyricists_id: APKHA37
lyricists_id: ILENG54
lyricists_id: PJLUT15
lyricists_id: MWILA76
actors_name: Khawaja, Anthony
actors_id: APKHA37
actors_role: owner
full_text_status: public
publication: Ophthalmology
volume: 126
number: 3
pagerange: 393-406
event_location: United States
issn: 0161-6420
citation:        Colijn, JM;    Hollander, AID;    Demirkan, A;    Cougnard-Grégoire, A;    Verzijden, T;    Kersten, E;    Meester, MA;                                                                                                             ... E3 Consortium and EYE-RISK Consortium, .; + view all <#>        Colijn, JM;  Hollander, AID;  Demirkan, A;  Cougnard-Grégoire, A;  Verzijden, T;  Kersten, E;  Meester, MA;  Merle, BMJ;  Papageorgiou, G;  Ahmad, S;  Mulder, MT;  Costa, MA;  Benlian, P;  Bertelsen, G;  Bron, A;  Claes, B;  Creuzot-Garcher, C;  Erke, MG;  Fauser, S;  Foster, PJ;  Hammond, CJ;  Hense, HW;  Hoyng, CB;  Khawaja, AP;  Korobelnik, J;  Piermarocchi, S;  Segato, T;  Silva, R;  Souied, EH;  Williams, KM;  van Duijn, CM;  Delcourt, C;  Klaver, CCW;  E3 Consortium and EYE-RISK Consortium, .;   - view fewer <#>    (2019)    Increased High Density Lipoprotein-levels associated with Age-related Macular degeneration. Evidence from the EYE-RISK and E3 Consortia.                   Ophthalmology , 126  (3)   pp. 393-406.    10.1016/j.ophtha.2018.09.045 <https://doi.org/10.1016/j.ophtha.2018.09.045>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10058812/1/Lipiden%20paper.pdf