[HTML][HTML] A mitochondrial genome-wide association study of cataract in a Latino population
Translational Vision Science & Technology, 2020•arvojournals.org
Purpose: Over 9.5 million Latinos could be affected by cataracts by 2050. However, no
known cataract genetic risk alleles have been identified in Latinos. Moreover, no
mitochondrial genome-wide association studies (MiWAS) have been conducted on cataracts
in a Latino cohort despite the association between mitochondrial dysfunction and cataracts.
Our purpose was to identify a mitochondrial DNA variant that associated with cataracts in a
large-scale Latino population. Methods: We conducted an MiWAS to identify mitochondrial …
known cataract genetic risk alleles have been identified in Latinos. Moreover, no
mitochondrial genome-wide association studies (MiWAS) have been conducted on cataracts
in a Latino cohort despite the association between mitochondrial dysfunction and cataracts.
Our purpose was to identify a mitochondrial DNA variant that associated with cataracts in a
large-scale Latino population. Methods: We conducted an MiWAS to identify mitochondrial …
Abstract
Purpose: Over 9.5 million Latinos could be affected by cataracts by 2050. However, no known cataract genetic risk alleles have been identified in Latinos. Moreover, no mitochondrial genome-wide association studies (MiWAS) have been conducted on cataracts in a Latino cohort despite the association between mitochondrial dysfunction and cataracts. Our purpose was to identify a mitochondrial DNA variant that associated with cataracts in a large-scale Latino population.
Methods: We conducted an MiWAS to identify mitochondrial single-nucleotide polymorphisms that modify cataract risk in nearly 3500 individuals enrolled in the Los Angles Latino Eye Study cohort, the largest Latino-specific cohort with comprehensive cataract data. Our analytic strategy for MiWAS included logistic regression on cataract occurrence while controlling for mitochondrial genetic ancestry, age, and biological sex.
Results: We found that MitoG228A (rs41323649) alternative allele carriers experienced a five times greater risk for cataracts compared with reference allele carriers. Alternative allele carriers also developed cataracts earlier in life compared with reference allele carriers. Intracohort cross-validation with 10-fold resampling and five repeats showed that the effect of MitoG228A remained significant.
Conclusions: MitoG228A increased risk for cataracts five-fold in approximately 3500 Latinos. To the best of our knowledge, this is the first cataract MiWAS on a large-scale Latino population. This association needs to be validated in an independent cohort.
Translational Relevance: Our discovery hypothesis-generating study suggest MitoG228A has potential to be used as a risk factor in the clinic and as a target for therapeutics. With validation via an independent cohort, MitoG228A could be used to estimate cataract risk for a Latino to reduce complications later in life.
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