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