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

  • Retinal Disorders
  • Published:
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Abstract

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.

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Acknowledgements

We thank all the volunteers who generously participated in this study and made this research possible.

Funding

This study was funded by contracts N01‐AG‐1‐2109 and HHSN271201600005C from the Intramural Research Program of the National Institute on Aging, National Institutes of Health (NIH).

Author information

Author notes

  1. Rita Serra and Andrea Angius contributed equally to this work.

Authors and Affiliations

  1. Institute of Genetic and Biomedical Research, National Research Council, Cittadella Universitaria Di Cagliari, c/o S.S 554 bivio per Sestu Km 4,500, 09042, Monserrato, Cagliari, Italy

    Rita Serra, Vincenzo Rallo, Maristella Steri, Maria Grazia Piras, Michele Marongiu, Edoardo Fiorillo & Andrea Angius

  2. Department of Biomedical Sciences, University of Sassari, Sassari, Italy

    Rita Serra & Francesco Cucca

  3. Centre Ophtalmologique de L’Odeon, 113 bd Saint Germain, 75006, Paris, France

    Rita Serra & Florence Coscas

  4. Department of Medicine, Surgery and Pharmacy, Ophthalmology Unit, University of Sassari, Sassari, Italy

    Antonio Pinna

  5. Laboratory of Genetics and Genomics, National Institute On Aging, Baltimore, MD, USA

    Myriam Gorospe & David Schlessinger

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  1. Rita Serra
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Correspondence to Rita Serra or Andrea Angius.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the (place name of institution and/or national research committee) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Rita Serra and Vincenzo Rallo are joint first authors.

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Serra, R., Rallo, V., Pinna, A. et al. Polygenic risk score and biochemical/environmental variables predict a low-risk profile of age-related macular degeneration in Sardinia. Graefes Arch Clin Exp Ophthalmol 261, 691–698 (2023). https://doi.org/10.1007/s00417-022-05858-5

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