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A Mitochondrial Genome-Wide Association Study of Cataract in a Latino Population.

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.

SUBMITTER: Miller B

PROVIDER: S-EPMC7408807 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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A Mitochondrial Genome-Wide Association Study of Cataract in a Latino Population.

Miller Brendan B Torres Mina M Jiang Xuejuan X McKean-Cowdin Roberta R Nousome Darryl D Kim Su-Jeong SJ Mehta Hemal H HH Yen Kelvin K Cohen Pinchas P Varma Rohit R

Translational vision science & technology 20200523 6

<h4>Purpose</h4>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.<h4>Methods</h4>We condu ...[more]

PMID: 32821522

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Project description:ObjectivesRecent genome-wide association studies (GWASs) have identified numerous putative genetic polymorphisms associated with bipolar disorder (BD) and/or schizophrenia (SC). We hypothesized that a portion of these polymorphisms would also be associated with BD in the Latino American population. To identify such regions, we tested previously identified genetic variants associated with BD and/or SC and ancestral haploblocks containing these single nucleotide polymorphisms (SNPs) in a sample of Latino subjects with BD.MethodsA total of 2254 Latino individuals were genotyped for 91 SNPs identified in previous BD and/or SC GWASs, along with selected SNPs in strong linkage disequilibrium with these markers. Family-based single marker and haplotype association testing was performed using the PBAT software package. Empirical P-values were derived from 10 000 permutations.ResultsAssociations of eight a priori GWAS SNPs with BD were replicated with nominal (P≤.05) levels of significance. These included SNPs within nuclear factor I A (NFIA), serologically defined colon cancer antigen 8 (SDCCAG8), lysosomal associated membrane protein 3 (LAMP3), nuclear factor kappa B subunit 1 (NFKB1), major histocompatibility complex, class I, B (HLA-B) and 5'-nucleotidase, cytosolic II (NT5C2) and SNPs within intragenic regions microRNA 6828 (MIR6828)-solute carrier family 7 member 14 (SLC7A14) and sonic hedgehog (SHH)-long intergenic non-protein coding RNA 1006 (LINC01006). Of the 76 ancestral haploblocks that were tested for associations with BD, our top associated haploblock was located in LAMP3; however, the association did not meet statistical thresholds of significance following Bonferroni correction.ConclusionsThese results indicate that some of the gene variants found to be associated with BD or SC in other populations are also associated with BD risk in Latinos. Variants in six genes and two intragenic regions were associated with BD in our Latino sample and provide additional evidence for overlap in genetic risk between SC and BD.

Dataset Information

A Mitochondrial Genome-Wide Association Study of Cataract in a Latino Population.

Publications

A Mitochondrial Genome-Wide Association Study of Cataract in a Latino Population.

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