Comparison of risk allele frequencies of single nucleotide polymorphisms associated with age-related macular degeneration in different ethnic groups

Abstract

Background: The prevalence of age-related macular degeneration (AMD) varies from 6.8 to 18.3% for all forms of AMD and from 0.6 to 2.6% for late AMD according to race, suggesting the existence of genetic differences among races. The purpose of this study was to determine the genetic causes of differences in the prevalence of AMD among individuals of different races.

Methods: We collected 138 AMD-associated single nucleotide polymorphisms (SNPs) from a genome-wide association studies catalog. Their population-level allele frequencies were derived based on the 1000 Genomes Project and Korean Reference Genome Database. We used Fisher's exact tests to assess whether the effect allele at a given SNP was significantly enriched or depleted in the database.

Results: European, American, and South Asian populations showed similar heatmap patterns, whereas East Asian, and Korean populations had distinct patterns. Korean populations exhibited patterns that were different from those of the other groups; rs5754227 (SYN3), rs1626340 (TGFBR1/COL15A1), rs3750846(ARMS2/HTRA1), and rs9564692 (B3GALTL) were enriched, whereas rs2230199 (C3) and rs73036519 (EXOC3L2/MARK4) were depleted in Koreans; these SNPs are associated with late AMD. The genetic risk score calculated from allele frequencies was not less in East Asians than in Europeans.

Conclusion: The prevalence of AMD is lower in Asians than in Europeans. However, our study showed that genetic risk scores in East Asians were similar to those in Europeans, which may explain why the global projected number of people with AMD by 2040 is in largest for East Asians, including Koreans.

Keywords: Age-related macular degeneration; Allele frequency; Genetic risk scores; Prevalence; Single nucleotide polymorphism.

Fig. 1

Comparison of the frequency of age-related macular degeneration (AMD)-related single nucleotide polymorphisms (SNPs) according to super population. AMR: American, EUR: European, SAS: South Asian, AFR: African, EAS: East Asian, KOR: Korean

Fig. 2

Heatmap generated using single nucleotide polymorphisms related to late age-related macular degeneration in the global population. Each row shows an SNP, and each column shows a continent. Red color indicates that the effect allele is enriched, whereas purple color indicates that the effect allele is depleted. AMR: American, EUR: European, SAS: South Asian, AFR: African, EAS: East Asian, KOR: Korean

Fig. 3

Heatmap generated using single nucleotide polymorphisms related to late age-related macular degeneration in the East Asian population. Each row shows an SNP, and each column shows a continent. Red color indicates that the effect allele is enriched, whereas purple color indicates that the effect allele is depleted. CDX: Chinese Dai in Xishuangbanna; CHB: Han Chinese in Beijing, China; CHS: Southern Han Chinese, China; JPT: Japanese in Tokyo, Japan; KOR: Korean in the Republic of Korea; KHV: Kinh in Ho Chi Minh City, Vietnam

Fig. 4

Genetic risk score calculations of age-related macular degeneration for any AMD or late AMD using related single nucleotide polymorphisms. ACB: African Caribbean in Barbados; ASW: African ancestry in the Southwest USA; BEB: Bengali in Bangladesh; CDX: Chinese Dai in Xishuangbanna; CEU: Utah residents with Northern and Western European ancestry; CHB: Han Chinese in Beijing, China; CHS: Southern Han Chinese, China; CLM: Colombian in Medellin, Colombia; ESN: Esan in Nigeria; FIN: Finnish in Finland; GBR: British in England and Scotland; GIH: Gujarati Indian in Houston, TX, USA; GWD: Gambian in Western Division, Gambia; IBS: Iberian populations in Spain; ITU: Indian Telugu in the UK; JPT: Japanese in Tokyo, Japan; KOR: Korean in the Republic of Korea; KHV: Kinh in Ho Chi Minh City, Vietnam; LWK: Luhya in Webuye, Kenya; MSL: Mende in Sierra Leone; MXL: Mexican ancestry in Los Angeles, CA, USA; PEL: Peruvian in Lima, Peru; PJL: Punjabi in Lahore, Pakistan; PUR: Puerto Rican in Puerto Rico; STU: Sri Lankan Tamil in the UK; TSI: Toscani in Italy; YRI: Yoruba in Ibadan, Nigeria

Fig. 5

Correlation plots of the prevalence of age-related macular degeneration (any or late) and genetic risk score using related single nucleotide polymorphisms. The graphs on the left and right indicate correlations of prevalence and genetic risk scores with any AMD and late AMD, respectively. The dotted line indicates the relationship between genetic risk score and prevalence (circular shape) for people with AMD who are 40 years old or older, and the solid line indicates the relationship between genetic risk score and prevalence of AMD (triangular shape) for people 65 years of age or older. AMR: American, EUR: European