Polygenic risk score and biochemical/environmental variables predict a low-risk profile of age-related macular degeneration in Sardinia

• Published in: Graefe's archive for clinical and experimental ophthalmology 2023-03, Vol.261 (3), p.691-698
• Main Authors: Serra, Rita, Rallo, Vincenzo, Pinna, Antonio, Steri, Maristella, Piras, Maria Grazia, Marongiu, Michele, Coscas, Florence, Gorospe, Myriam, Schlessinger, David, Fiorillo, Edoardo, Cucca, Francesco, Angius, Andrea
• Format: Article
• Language: English
• Subjects: Biomarkers; C-Reactive Protein; Color vision; Eye diseases; Fibrinogen; Humans; Inflammation; Macular degeneration; Macular Degeneration - diagnosis; Macular Degeneration - epidemiology; Macular Degeneration - genetics; Medicine; Medicine & Public Health; Ophthalmology; Retina; Retinal Disorders; Risk Assessment; Risk Factors
• ISSN: 0721-832X; 1435-702X; 1435-702X
• DOI: 10.1007/s00417-022-05858-5

Purpose To ascertain the prevalence and clinical and genetic features of age-related macular degeneration (AMD) in subjects living in the Lanusei valley, Central Sardinia, Italy, involved in a study on ageing (SardiNIA project). Methods A total of 814 volunteers aged ≥ 50 years, randomly selected from the SardiNIA project dataset, were included. A color fundus (CF) photograph of the 30° central retina of each eye was obtained and graded according to the Age-Related Eye Disease Study system. Life-style choices were investigated using standardized questionnaires. The concentrations of several inflammatory biomarkers (i.e., complement component, fibrinogen, and C-reactive protein) were measured. Polygenic risk score (PRS) was calculated and compared with results obtained from a European cohort. Results A total of 756 subjects had gradable CF photographs for AMD detection. In 91.3%, no signs of AMD were observed. The prevalence rates of early and late AMDs were 6.9% and 0.6%, respectively. A total of 85% of subjects were physically active; only 13.5% were current smokers. Low concentrations of complement component, fibrinogen, and C-reactive protein were found. We calculated the polygenic risk scores (PRS) using 40 AMD markers distributed on several candidate genes in Europeans and Sardinians. The mean PRS value was significantly lower in Sardinians than in the Europeans (0.21 vs. 0.248, respectively, p  = 1.18 × 10 −77 ). Conclusions In our cohort, most subjects showed no sign of any AMD type and late AMD was a condition rarely observed. Results of genetic, biochemical, and life-style investigation support the hypothesis that Sardinia population may present of a peculiar background with a protective effect against AMD development.