Genome-wide Scan of African-American and White Families for Linkage to Myopia

doi:10.1016/j.ajo.2008.09.004

American Journal of Ophthalmology

Volume 147, Issue 3, March 2009, Pages 512-517.e2

https://doi.org/10.1016/j.ajo.2008.09.004 Get rights and content

Purpose

To identify myopia susceptibility genes influencing common myopia in 94 African-American and 36 White families.

Design

A prospective study of families with myopia consisting of a minimum of two individuals affected with myopia.

Methods

Extended families consisting of at least two siblings affected with myopia were ascertained. A genome-wide linkage scan using 387 markers was conducted by the Center for Inherited Disease Research. Linkage analyses were conducted with parametric and nonparametric methods. Model-free linkage analysis was performed maximizing over penetrance and over dominance (that is, fitting a wide range of both dominant and recessive models).

Results

Under the model-free analysis, the maximum two point heterogeneity logarithm of the odds score (MALOD) was 2.87 at D6S1009 in the White cohort and the maximum multipoint MALOD was 2.42 at D12S373-D12S1042 in the same cohort. The nonparametric linkage (NPL) maximum multipoint at D6S1035 had a P value of .005. An overall multipoint NPL score was obtained by combining NPL scores from both populations. The highest combined NPL score was observed at D20S478 with a significant P value of .008. Suggestive evidence of linkage in the White cohort mapped to a previously mapped locus on chromosome 11 at D11S1981 (NPL = 2.14; P = .02).

Conclusions

Suggestive evidence of linkage to myopia in both African Americans and Whites was seen on chromosome 20 and became more significant when the scores were combined for both groups. The locus on chromosome 11 independently confirms a report by Hammond and associates mapping a myopia quantitative trait locus to this region.

Section snippets

Family Screening

The identification of myopic families was accomplished through mailings, eye clinic interviews, and referrals from private optometrists and ophthalmologists. In order to be eligible to participate in the study, families had to satisfy the following criteria: 1) At least three participating family members; 2) only one myopic parent, and 3) at least two myopic siblings. Medical records were obtained for each consenting member of selected families and/or refractions were obtained when records were

Results

A total of 94 African-American and 36 White families were analyzed for linkage to myopia (Table 1). The average family size for the African-American population was five, with five families having more than 10 members. The mean family size in the White group was 7.2, and seven families had more than 10 members each. The average refractive error (D) was similar in both populations.

Initial NPL analyses were performed for both the African-American and White data since the modes of inheritance for

Discussion

We observed several regions of suggestive evidence for linkage to myopia in these data. The most interesting of these regions is on chromosome 20, around 47 to 62 cM, where suggestive evidence for linkage was seen in both African-American and White families. The local linkage peaks in these subgroups were approximately 7 cM apart. Moreover, the combined analysis of the two populations resulted in nonparametric multipoint linkage scores with minimum P values between .007 and .008. Hence, the

References (34)

R.A. Weale
Epidemiology of refractive errors and presbyopia
Surv Ophthalmol
(2003)
D. Stambolian et al.
Genome-wide linkage scan for myopia susceptibility loci among Ashkenazi Jewish families shows evidence of linkage on chromosome 22q12
Am J Hum Genet
(2004)
C.J. Hammond et al.
A susceptibility locus for myopia in the normal population is linked to the PAX6 gene region on chromosome 11: a genome-wide scan of dizygotic twins
Am J Hum Genet
(2004)
D. Stambolian et al.
Genome-wide scan for myopia in the old order Amish
Am J Ophthalmol
(2005)
M. Boehnke et al.
Accurate Inference of Relationships in Sib-Pair Linkage Studies
Am J Hum Genet
(1997)
D. Reich et al.
Admixture mapping of an allele affecting interleukin 6 soluble receptor and interleukin 6 levels
Am J Hum Genet
(2007)
M.G. Villarreal et al.
Myopisation: the refractive tendency in teenagersPrevalence of myopia among young teenagers in Sweden
Acta Ophthalmol Scand
(2000)
B. Junghans et al.
Referral rates for a functional vision screening among a large cosmopolitan sample of Australian children
Ophthalmic Physiol Opt
(2002)
S.M. Saw
A synopsis of the prevalence rates and environmental risk factors for myopia
Clin Exp Optom
(2003)
S. Resnikoff et al.
Blindness prevention programmes: past, present, and future
Bull World Health Organ
(2001)

W.C. Tang et al.

A review of current approaches to identifying human genes involved in myopia

Clin Exp Optom

(2008)

D. Stambolian et al.

Genome-wide scan of additional Jewish families confirms linkage of a myopia susceptibility locus to chromosome 22q12

Mol Vis

(2006)

R. Wojciechowski et al.

Genome-wide scan in Ashkenazi Jewish families demonstrates evidence of linkage of ocular refraction to a QTL on chromosome 1p36

Hum Genet

(2006)

A.P. Klein et al.

Confirmation of linkage to ocular refraction on chromosome 22q and identification of a novel linkage region on 1q

Arch Ophthalmol

(2007)

E. Ciner et al.

Genomewide scan of ocular refraction in African-American families shows significant linkage to chromosome 7p15

Genet Epidemiol

(2008)

D.L. Duffy

Sibpair: a program for nonparametric linkage/association analysis

A. Young

GAS, version 2.3

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Original articleGenome-wide Scan of African-American and White Families for Linkage to Myopia

Purpose

Design

Methods

Results

Conclusions

Section snippets

Family Screening

Results

Discussion

Surv Ophthalmol

Am J Hum Genet

Am J Hum Genet

Am J Ophthalmol

Am J Hum Genet

Am J Hum Genet

Myopisation: the refractive tendency in teenagersPrevalence of myopia among young teenagers in Sweden

Acta Ophthalmol Scand

Referral rates for a functional vision screening among a large cosmopolitan sample of Australian children

Ophthalmic Physiol Opt

A synopsis of the prevalence rates and environmental risk factors for myopia

Clin Exp Optom

Blindness prevention programmes: past, present, and future

Bull World Health Organ

A review of current approaches to identifying human genes involved in myopia

Clin Exp Optom

Genome-wide scan of additional Jewish families confirms linkage of a myopia susceptibility locus to chromosome 22q12

Mol Vis

Genome-wide scan in Ashkenazi Jewish families demonstrates evidence of linkage of ocular refraction to a QTL on chromosome 1p36

Hum Genet

Confirmation of linkage to ocular refraction on chromosome 22q and identification of a novel linkage region on 1q

Arch Ophthalmol

Genomewide scan of ocular refraction in African-American families shows significant linkage to chromosome 7p15

Genet Epidemiol

Sibpair: a program for nonparametric linkage/association analysis

GAS, version 2.3

Original article
Genome-wide Scan of African-American and White Families for Linkage to Myopia