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Exome genotyping and linkage analysis identifies two novel linked regions and replicates two others for myopia in Ashkenazi Jewish families.
Simpson, Claire L; Musolf, Anthony M; Li, Qing; Portas, Laura; Murgia, Federico; Cordero, Roberto Y; Cordero, Jennifer B; Moiz, Bilal A; Holzinger, Emily R; Middlebrooks, Candace D; Lewis, Deyana D; Bailey-Wilson, Joan E; Stambolian, Dwight.
Affiliation
  • Simpson CL; Department of Genetics, Genomics and Informatics and Department of Ophthalmology, University of Tennessee Health Science Center, 71 S. Manassas Room 417, Memphis, TN, 38163, USA.
  • Musolf AM; Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Dr., Suite 1200, Baltimore, MD, 21224, USA.
  • Li Q; Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Dr., Suite 1200, Baltimore, MD, 21224, USA.
  • Portas L; Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Dr., Suite 1200, Baltimore, MD, 21224, USA.
  • Murgia F; Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Dr., Suite 1200, Baltimore, MD, 21224, USA.
  • Cordero RY; Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Dr., Suite 1200, Baltimore, MD, 21224, USA.
  • Cordero JB; Department of Genetics, Genomics and Informatics and Department of Ophthalmology, University of Tennessee Health Science Center, 71 S. Manassas Room 417, Memphis, TN, 38163, USA.
  • Moiz BA; Department of Genetics, Genomics and Informatics and Department of Ophthalmology, University of Tennessee Health Science Center, 71 S. Manassas Room 417, Memphis, TN, 38163, USA.
  • Holzinger ER; Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Dr., Suite 1200, Baltimore, MD, 21224, USA.
  • Middlebrooks CD; Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Dr., Suite 1200, Baltimore, MD, 21224, USA.
  • Lewis DD; Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Dr., Suite 1200, Baltimore, MD, 21224, USA.
  • Bailey-Wilson JE; Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Dr., Suite 1200, Baltimore, MD, 21224, USA.
  • Stambolian D; Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Dr., Suite 1200, Baltimore, MD, 21224, USA. jebw@mail.nih.gov.
BMC Med Genet ; 20(1): 27, 2019 01 31.
Article in En | MEDLINE | ID: mdl-30704416
ABSTRACT

BACKGROUND:

Myopia is one of most common eye diseases in the world and affects 1 in 4 Americans. It is a complex disease caused by both environmental and genetics effects; the genetics effects are still not well understood. In this study, we performed genetic linkage analyses on Ashkenazi Jewish families with a strong familial history of myopia to elucidate any potential causal genes.

METHODS:

Sixty-four extended Ashkenazi Jewish families were previously collected from New Jersey. Genotypes from the Illumina ExomePlus array were merged with prior microsatellite linkage data from these families. Additional custom markers were added for candidate regions reported in literature for myopia or refractive error. Myopia was defined as mean spherical equivalent (MSE) of -1D or worse and parametric two-point linkage analyses (using TwoPointLods) and multi-point linkage analyses (using SimWalk2) were performed as well as collapsed haplotype pattern (CHP) analysis in SEQLinkage and association analyses performed with FBAT and rv-TDT.

RESULTS:

Strongest evidence of linkage was on 1p36(two-point LOD = 4.47) a region previously linked to refractive error (MYP14) but not myopia. Another genome-wide significant locus was found on 8q24.22 with a maximum two-point LOD score of 3.75. CHP analysis also detected the signal on 1p36, localized to the LINC00339 gene with a maximum HLOD of 3.47, as well as genome-wide significant signals on 7q36.1 and 11p15, which overlaps with the MYP7 locus.

CONCLUSIONS:

We identified 2 novel linkage peaks for myopia on chromosomes 7 and 8 in these Ashkenazi Jewish families and replicated 2 more loci on chromosomes 1 and 11, one previously reported in refractive error but not myopia in these families and the other locus previously reported in the literature. Strong candidate genes have been identified within these linkage peaks in our families. Targeted sequencing in these regions will be necessary to definitively identify causal variants under these linkage peaks.
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Full text: 1 Database: MEDLINE Main subject: Jews / Chromosomes, Human / Genotyping Techniques / Myopia Type of study: Prognostic_studies Limits: Female / Humans / Male Language: En Journal: BMC Med Genet Journal subject: GENETICA MEDICA Year: 2019 Type: Article Affiliation country: United States
Fulltext
Add to My VHL
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PubMed Links
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Full text: 1 Database: MEDLINE Main subject: Jews / Chromosomes, Human / Genotyping Techniques / Myopia Type of study: Prognostic_studies Limits: Female / Humans / Male Language: En Journal: BMC Med Genet Journal subject: GENETICA MEDICA Year: 2019 Type: Article Affiliation country: United States