RT Journal Article
A1 Miller, Brendan
A1 Torres, Mina
A1 Jiang, Xuejuan
A1 McKean-Cowdin, Roberta
A1 Nousome, Darryl
A1 Kim, Su-Jeong
A1 Mehta, Hemal H.
A1 Yen, Kelvin
A1 Cohen, Pinchas
A1 Varma, Rohit
T1 A Mitochondrial Genome-Wide Association Study of Cataract in a Latino Population
JF Translational Vision Science & Technology
JO Trans. Vis. Sci. Tech.
YR 2020
DO 10.1167/tvst.9.6.25
VO 9
IS 6
SP 25
OP 25
SN 2164-2591
AB    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.    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.    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.    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.    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.  
RD 11/27/2020
UL https://doi.org/10.1167/tvst.9.6.25