Identification of genome-wide copy number variations and a family-based association study of Avellino corneal dystrophy.
OBJECTIVE
To determine the association of identified copy number variations (CNVs) in whole genome with the risk of Avellino corneal dystrophy (ACD) in a Korean population.


METHODS
Case-control study.


METHODS
A total of 146 patients with ACD and 226 control subjects.


METHODS
A total of 193 trios were genotyped by the Illumina HumanHapCNV370-Duo BeadChip (370,404 markers) (Illumina, Inc., San Diego, CA). The intensity signal (log R ratio) and allelic intensity ratio (B allele frequency) of each marker in all individuals were obtained by Illumina BeadStudio software (Illumina, Inc.). To obtain authentic CNVs in this study, we performed a family-based CNV validation and family-based boundary mapping using the PennCNV algorithm, which incorporates multiple factors, including total log R ratio, B allele frequency, and family information, based on an integrated hidden Markov model.


METHODS
Statistical comparison and identification of CNVs between case and control using family information.


RESULTS
We identified 27,267 individual trio CNVs with a median size of 16.2 kb, aggregated in 2245 CNV regions. Most of the identified trio CNVs in this study showed well-defined CNV boundaries and overlapped with those in the Database of Genomic Variants (DGV) (83.4% in number and 79.2% in length). With the common CNV regions (264 CNV regions >5%), we performed a family-based association test with the risk of ACD.


CONCLUSIONS
Two CNV regions (chr6:29978470-29987783 and chr14:59896944-59916129) were significantly associated with the risk of ACD (P=0.05-0.003 and P=0.008, respectively). This study describes the first results of a genome-wide association analysis of individual CNVs with the risk of ACD and shows that 2 novel CNV loci may be involved in the risk of ACD.


BACKGROUND
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Bae
Joon Seol
JS
Laboratory of Genomic Diversity, Department of Life Science, Sogang University, Shinsu-dong, Mapo-gu, Seoul, Republic of Korea.
Cheong
Hyun Sub
HS
Chun
Ji-Yong
JY
Park
Tae Joon
TJ
Kim
Ji-On
JO
Kim
Eun Mi
EM
Park
Miey
M
Kim
Dong-Joon
DJ
Lee
Eun-Ju
EJ
Kim
Eung Kweon
EK
Lee
Jong-Young
JY
Shin
Hyoung Doo
HD
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007723:Korea / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018570:Risk Assessment