TW201011107A - Method of determining susceptibility of myopia, method of screening myopia therapeutic agent, and method of assessing probability of response to a myopia therapeutic agent - Google Patents

Abstract

Using the BICD1 gene as a marker for diagnosing myopia and/or myopia related complications is provided. The method includes obtaining a biological sample from a subject, and determining at least one SNP genotype in the BICD1 gene in the biological sample, wherein the presence of the SNP genotype indicates that the subject is susceptible to myopia. The SNP genotype is selected from the group consisting of SNPs rs7966276, rs1151029, rs2650122, and rs10771923. In addition, the present invention also provides a method of screening a material for preventing, treating myopia, and a method of assessing a subject for probability of response to a myopia therapeutic agent.

Description

201011107 VI. Description of the Invention: [Technical Field of the Invention] The present invention relates to a method for detecting myopia, and particularly relates to a single nucleotide polymorphism (SNP) for detecting BICD1 gene. Methods of myopia and/or myopia-related complications. Furthermore, the present invention is more related to a method of screening for treating or inhibiting myopia. ❹ [Prior Art] Myopia refers to the fact that in the case of relaxation, parallel rays parallel to the visual axis converge in front of the retina through the refraction of the eyeball refractive system, which is a kind of refractive error. When a person with myopia looks at a distant object, it cannot be clearly imaged on the retina, so that the image is focused on the vitreous of the eyeball, not on the retina. Myopia is widely present in the world, and the treatment of myopia is related to ethnicity, gender, and age (Invest Ophthalmol Vis Sci 1997; 38: 334-40; Optom Vis Sci 2001; 78: 234-9; J Formos Med Assoc 2001; :684-91). In the United States, 25% of people between the ages of 12 and 54 suffer from myopia (Arch Ophthalmol 1983; 101: 405-7), and the rate of whites suffering from myopia (28.1%) is higher than that of African-Americans (19.4%) (Invest Ophthalmol Vis Sci 1997; 38: 334-40). In all myopic populations, the proportion of high myopia (diopter < -5.0 D) is 27% to 33%, and the prevalence is 1.7% to 2 ° / 〇 (Arch Ophthalmol 1983; 101: 405-7). In the world, Taiwan is a high-risk area that belongs to myopia. If diopter < -6.0 D is used as high myopia, Taiwan has a higher proportion of high myopia than Asian countries, and 18% of male students and 24% of female students in Taiwan suffer from myopia (J Formos Med Assoc 2001;100:684 -91), this ratio is even higher

0911-A51298-TW 4 201011107 The proportion of young people in Singapore (131%) (〇pt〇m Vis Sci 2001; 78:234-9), found in the national surveys in 1995 and 2000, the prevalence of myopia in Taiwan is still Continued to increase. High myopia can cause blindness, for example, it is associated with retinal detachment, yellow spot degeneration, and glaucoma. 5.6% of all blind children in the United States are related to myopia. Although myopia can be treated or corrected by glasses, contact lenses, Orthokeratology, and Laser Refractive Surgery (LASIK), none of the above methods can inhibit retinal detachment, yellow spot degradation, and glaucoma due to myopia complications. . In addition, excessive use of contact lenses (Curr Opin Ophthalmol 1998; 9: 66-71), Orthokeratology (J Refract Surg 2003; 195247-9) and other surgical procedures may also increase the risk of complications in the eye. In the United States, it is necessary to spend 250 million to treat myopia each year (Arch Ophthalmol 1994; 112: 1526-30). Many environmental factors have been shown to be associated with myopia, and twin studies have shown a relationship between myopia and heredity. Family heritability is estimated to be between 58% and 90% (Invest Ophthalmol Vis Sci 2001; 42:1232-6; Genet Epidemiol 1988; 5: 171-81; Hum Hered 1971; 41: 151-6; Br J Ophthalmol 2001; 85: 1470-6). Experiments have confirmed that family history is an important cause of high myopia (Invest Ophthalmol Vis Sci 2004; 45: 3446-52; Optom Vis Sci 1996; 73: 279-82; JAMA 1994; 271:1323-7; Invest Ophthalmol Vis Sci 2002; : 3633-40; Optom Vis Sci 1999; 76: 387-92; Invest Ophthalmol Vis Sci 2004; 45: 2873-8). However, only a few studies have found genes associated with myopia, but no evidence of large data has been obtained. Therefore, medically, a biological standard is needed as a reference for detecting and treating 0911-A51298-TW 5 201011107 and slowing down myopia and its complications. SUMMARY OF THE INVENTION The present invention provides a method of determining whether a body is susceptible to myopia, comprising: obtaining a biological sample from the individual, and determining at least one single nucleotide polymorphism of the BICD1 gene in the biological sample. (SNP) 'The presence of a dangerous genotype of this single nucleotide polymorphism indicates that the individual is susceptible to myopia. The invention further provides a method for screening for inhibiting or treating myopia and/or myopia-related complications, comprising contacting a test substance and a cell expressing the BICD1 gene, and screening a substance compared to a control group This substance has the ability to regulate the expression of the BICD1 gene. The present invention further provides a method for assessing the response of a body to a myopia treatment agent, comprising determining a single nucleotide polymorphism of a BICD1 gene, wherein when the genotype of the single nucleotide polymorphism is present, The individual has a good response (positive reaction) to the myopia treatment agent. The invention further provides a kit for detecting myopia susceptibility comprising: one or a plurality of reagents, a buffer, and an enzyme for detecting mononuclear acid polymorphism of one or more BICD1 genes. The above and other objects, features, and advantages of the present invention will become more apparent and understood. In an embodiment, the present invention provides a method for determining whether a body is susceptible to myopia, comprising obtaining a biological sample from a body to detect at least one SNP of the BICD1 gene in the biological sample (single

0911-A51298-TW 201011107 nucleotide polymorphism), wherein the presence of this SISfP genotype indicates that the individual has near vision sensitivity. This SNP genotype was selected from the following subgroups: SNPsrs7966276, rsll51029, rs2650122 and rsl0771923. The variation of this genotype may be a change in the sequence of a BICD1 gene', e.g., may be a single nucleotide change that may alter the peptide encoding the BICD1 gene, resulting in different translations or causing transcriptional function of the gene to be affected. In the present invention, whether a genotype susceptible to myopia and/or myopia-related complications is present, primer extension methods (for example, PinPoint analysis, MassextendTM, SPC-SBE, or GOOD analysis), hybridization methods (eg, ' TaqMan analysis, bead arry, or SNP wafers, ligation (eg, compositional green fluorescent transfer marker (CFFr tagS)), and enzyme cleavage (RFLP, Invader® analysis), PCR-SSCP (single chain) Conformation polymorphism) 'MRD (mismatch repair dection), BeadArrayTM, or SNPlexTM. First, a biological sample containing nucleotides (DNA) is collected or collected from one body. The subject of the present invention may be a mammal, preferably a human or individual suffering from myopia and/or myopia-related complications. Beta Individuals of the invention include, but are not limited to, adults, young children or infants. The biological sample of the present invention may be collected or isolated from any source having chromosomal DNA. The so-called source includes blood, amniotic fluid, cerebrospinal fluid, or tissue fluid of the skin, muscle, oral mucosa, placenta, gastrointestinal tract or other organs. Then, 'analyze the presence of bicDI genotypes in my DNA samples that are prone to myopia. In one embodiment of the invention, the BICD1 genotype can be identified by TaqMaii technology. Briefly, PCR primers and TaqMan MGB probes were designed using primer Express version 2.0, reacted in a GeneAmp 9700 thermal reaction cell and a 96-well plate, and utilized.

0911-A51298-TW 201011107

ABI Prism 7500 Sequence Debt Measurement System and ABI Prism 7500 SDS software version 1. (H Measure and analyze fluorescence intensity. In another embodiment, genotyping can be used to identify SNP genotypes, related processes Refer to Mutat Res 2005; 573:70-82 for the analysis of genotyping using Illumina BeadArray technology (Sentrix® Array Matrix) [Shen, 2005 #135]. Simply put, specific oligonucleotides (allelic specific) The oligonucleotide is conjugated to DNA, amplified by PCR, and hybridized by Cy-3 and Cy-5 primers for array hybridization and genotyping analysis. In another embodiment, a commercially available gene chip can be used. To identify the genotype of the SNP in the BICD1 gene. For example, the Affymetrix GeneChip® Human Mapping 500K array kit consists of two arrays, each of which can analyze approximately 250, one SNPs, which are hybridized by conventional methods. The BRLMM clustering algorithm is used to analyze the genotype. In addition, if the gene mutation (diversity) causes the production or disappearance of the restriction enzyme cleavage site, it can also be cut by restriction enzymes. (Digestion) to identify each genotype of the BICD1 gene. First, PCR is used to amplify the BICD1 basal factor in the biological sample. Then an RFLP analysis is performed. The cleavage of the DNA fragment can indicate the presence or absence of a specific BICD1 genotype, and further The relationship between the presence or absence of each genotype and myopia is known. In another embodiment, each SNP genotype of the BICD1 gene can be identified by sequence analysis (sequencing). First, use PCR or other appropriate methods to amplify. BICD1 gene or nucleotide, followed by analysis of the sequence of BICD1 nucleotide, BICD1 nucleotide fragment, BICD1 gene DNA, BICD1 gene DNa fragment by a conventional procedure, and comparing the above nucleotides/nuclei The difference between the nucleotide fragment or the genomic DNA/DNA fragment and the known BICD1 gene sequence.

0911-A51298-TW 8 201011107 = The presence of this individual represents a myopia and/or myopia-related complications. This artist can choose different methods to dream about the SNP of the mcm gene, and the skilled person can easily ^ And the above method or other methods are performed. "Myopia susceptibility" as used in the present invention means that the individual is susceptible to or not easy to be close when a certain genotype of the SNP of the present invention is present. The "low myopia susceptibility" as used in the present invention means that the individual is not susceptible to myopia when a certain genotype of the SNP of the present invention is present. The "high myopia susceptibility" as described in the present invention means When the genotype of the invention exists, the individual is prone to myopia. In one embodiment of the invention, when SNP rsl0771923 has a dual gene G genotype, or sNp rsl151029 has a dual gene T genotype, this is indicated Individuals are more prone to myopia, and their risk of developing myopia is at least 1.2 times higher than other genotypes. In another embodiment of the invention, when SNp rs7966276 has a genotype of dual gene A, it indicates that the individual is less prone to myopia, The risk of myopia is at least 0.6 times lower than other genotypes. It should be noted that this individual may also increase or decrease the risk of myopia due to other factors, such as diseases or the environment. In one embodiment, the present invention provides a substance (candidate drug) for screening for complications related to myopia and/or myopia, including a substance to be tested and a BICD1 group. The cells are contacted and screened for substances that regulate the BICD1 gene compared to the control group (cells not exposed to the drug candidate). The genotype of the BICD1 gene (eg, SNP rs7966276, rsll51029, rs2650122, and rsl0771923) can be used as a search or 0911-A51298-TW 9 201011107 Identify biomarkers for the treatment of myopia and/or myopia-related complications by screening for a substance that alters the expression of the BICD1 gene, such as 'exposed a cell to a test substance or a mixture The test substance composition (sequentially or simultaneously) is analyzed and the expression of the BICD1 gene of the cell is analyzed, and the BICD1 gene expression of the untreated and treated substance is compared. The test substance may be a known or unknown compound. Including, but not limited to, a compound, a small molecule drug, a poly-audio class, a nucleotide acid, a protein or a triumph, etc. For example, the test substance can be a small interfering RNA. In one embodiment of the invention, the test Substance can influence or regulate the BICD1 gene by the difference of SNP ® rsl0771923, SNP rsll51029 or SNP rs7966276 Preparing or slowing down myopia and/or myopia-related complications. In another embodiment of the invention, the invention further provides a method of treating, inhibiting or slowing the complications associated with myopia and/or myopia, comprising administering an effective one A myopia therapeutic agent (a myopia treatment drug) obtained by the above method. As described above, 'by controlling the performance or activity of the BICD1 gene can suppress or induce myopia and/or myopia-related complications. The drug can be used to treat or inhibit myopia and/or myopia-related complications by regulating the performance of the BICD1 gene. In another embodiment of the present invention, the present invention further provides a method for evaluating a drug for treating myopia, comprising analyzing an SNp of a BICD1 gene, a type, wherein the individual has a specific SNp genotype, indicating The drug may respond well to the treatment of myopia. In the method of the present invention, the gene marker (gene type) of the above BICD1 gene can be used as an evaluation of a body for myopia and/or myopia-related complications.

0911-A51298-TW 201011107 Sensitivity. When there is a SNP genotype that is susceptible to myopia in a body (for example, the dual gene G of 'rsl0771923, or the dual gene T of SNP rsll51029), this individual may have a good response to a myopia treatment. The "good response" of the present invention means that the individual has a better response to the myopia treatment drug than the individual without the specific SNP genotype, and the individual is also more susceptible to myopia and/or myopia. Related complication. In another embodiment of the present invention, the present invention further provides a kit for analyzing a biological sample obtained from a body and detecting the sensitivity of the individual to myopia. The set includes one or more reagents. To detect one or a plurality of SNP genotypes in the BICD1 gene. The "set" described in the present invention includes one or more SNp detection reagents, or one or a plurality of SNp detection reagents in one or more types ( For example, biological reagents, containers, packaging styles. The SNP detection kits of the invention include, but are not limited to, probe and primer combinations (eg, TaqMan probe/primer combinations) 'nucleotide arrays/microarrays, and A magnetic bead comprising one or more probes, primers or other detection reagents. The cartridge of the present invention can optionally include various electronic devices, such as arrays (DNA wafers) and microfluidic controls System ( "lab-on-a-chip" system) set of the present invention may comprise an electronic device 'and comprising - a plurality SNp or detection reagent.

The SNP detection kit typically includes one or more detection reagents, and other essential components (eg, buffers, enzymes such as DNA polymerase or iigases, strand extension nucleotides, eg, dNTPs, and Sanger_type DNA sequence reactions) , chain termination nucleotides, positive control sequences, negative control sequences and analogs thereof for analysis, for example, amplification and/or detection of an SNp nucleotide. The kit of the present invention may further comprise one or more devices for analyzing the mesh

0911-A51298-TW 201011107 The content of nucleotides, the difference between the target nucleotide and a standard content, and the instructions for use to explain how to use this kit to detect sNp nucleotide. In an embodiment of the invention, the kit of the invention includes all of the reagents required to detect one or more SNp nucleotides. In another embodiment of the invention, the 'SNP detection kit is a nucleotide array, or a compartmentalized kits, such as a microfluidic control system/"lab-on-a, chip" system. Any suitable probe, such as a dual gene-specific probe, can be used in the array (wafer) described above, and each probe or pair of probes can bind to a different dual gene position. Polynucleotide probes can be formed in specific regions using light directing chemistry procedures. Each DNA wafer can include, for example, a plurality (thousands to millions) of individual nucleotide probes arranged on a miniaturized lattice device. Preferably, the plurality of probes can be bonded to a solid support array. The kit of the present invention may comprise, for example, one or more reagents, a buffer, and an enzyme for detecting the SNp genotype of one or more BICD1. The reagent includes at least one substance for distinguishing and detecting the SNp 10 genotype, and the substance includes, but is not limited to, a nucleotide sequence which is completely complementary to a position of at least one BINP1 SNP genotype, A restriction enzyme (eg, an endonuclease) is used to identify a particular sequence, a calibrated primer or a calibrated even gene-specific probe. In an embodiment of the invention, the kit for detecting or diagnosing myopia of the present invention may comprise a plurality of primers for amplifying a region of the BICD1 gene, including SNPs rs7966276, rsi151029, rs2650122, and/or rsl0771923. When a SNP genotype with high myopia sensitivity is detected, it indicates that the individual is a high-risk group of myopia. Primers can be based on SNPs

0911-A51298-TW 12 201011107 rs7966276, rsll51029, rs265〇122 and/or sequences on both sides of 〇77 are designed. In addition, after analyzing the differences in the dual genes, mass spectrometers, fluorescence, or luminescence can be used to analyze differences in the dual genes. [Examples] 1. Gene Screening / This example was conducted on 4,000 subjects for myopia. The subjects can be broadly divided into four categories: (1) young males, (2) college students, (3) hospital staff, and (4) ophthalmic clinical patients. If the subject has a diopter of 2-6.0D' and the other eye has a diopter of €_4.〇1), it is classified as high myopia, and if the subject has a poor visual power, the diopter of one eye is _15 D, then The class was tested as a control group. All subjects were between the ages of 17 and 45 and were all Chinese. In the first step of the implementation, the Affymetrix GeneChip® Human Mapping 500K chipset is used, each consisting of 2 wafers, each wafer can be analyzed for approximately 25 〇, one SNP (Nsp wafer can analyze approximately 262,000 ' Sty wafers Analysis of 238,000). In order to maintain the DNA sample at a suitable quality 'to control the OD 260/280 value of all DNA samples between 1.7 and 2.0, and the OD260/230 value is greater than 1.0, take about 1.5 pg (30 μΐ of 50 ng/ The genotype DNA of μΐ) was genotyped and the BRLMM algorithm was used to obtain the results of the genotyping analysis. At the same time, in order to reduce the error, all analyses must meet the following conditions: a per sample call rate of at least 90% for each SNP, and a per SNP call rate of at least 90% for each sample. The secondary gene frequency for each SNP is at least 1% above, and the Hwar equilibrium is satisfied (p > 0.001). Based on the above results, SNPrs380619 is further divided into 0911-A51298-TW 13 201011107. The PLINK program (2m J i/ww Gewez1 2007; 81:559-75) was then used to calculate the genotype and dual gene frequencies, and the X2 test was performed to analyze the relationship between the dual gene, SNP genotype and high myopia. In order to analyze genotype relationships in various deportation modes, the obtained genotyping analysis data was placed into dominant, recessive, and additive modes, and a trend test was performed. Gene effects including various variables (gender and age) were introduced into the regression analysis, and the relationship between each SNP and diopter was analyzed using a linear regression model. Since the diopter greater than -3D is common in Taiwanese, subjects are divided into normal/moderate myopia (g-3D) and high myopia (S-6D), and logistic regression (Logistic Regression) ) Analyze phenotypes. Hap-clustering was used to analyze the haplotype. The preliminary analysis of this example showed the 10 most relevant SNPs, and the p value was at least 0.0002. The 10 SNPs are located on chromosomes 1, 2, 4, 6, 12, 16, 17, and 21, respectively, and are located at non-adjacent locations. ❹ 2. Second step of gene screening In the second step of the present embodiment, the 10 most relevant SNPs screened by the wafer are first used, and the 200 kb region at the front and rear ends of each SNP is regarded as a candidate region. In these 10 regions, we selected 384 SNPs and genotypes were identified in 1536 subjects. The diopter of this 1536 subjects was < -6 D or > - 1.5D, respectively. Genotyping is performed using Illumina BeadArray technology (Sentrix® Array Matrix) (Mutat Res 2005; 573:70-82), which utilizes DNA to interact with the dual 0911-A51298-TW 14 201011107 gene-specific oligonucleotide Bonded and amplified by PCR program. The hybridization procedure and gene mapping analysis of the wafers were performed using primers calibrated with Cy-3 and Cy-5, respectively. Each SNP was repeated 30 times to calculate the highest gene frequency. Overall, the success rate of gene identification in this second step was 97.1%. We found that the most relevant SNP (rs7966276) is located on the BICD1 gene of chromosome 12pll with a p-value of 1.13xUT04, and other SNPs in the BICD1 gene are also highly correlated (SNP rsll51029, p= 4.78xl0'4; SNP Rs2650122, p= 3.65xl0'2; see SNPrsl0771923, p=2.70xl0·2). 3. Third Step of Gene Screening In the third step, TaqMan technology (Applied Biosystems [ABI], Foster City, USA) was used to analyze the SNPs obtained by the second step. Briefly, PCR primers and TaqMan MGB probes were designed with Primer Express version 2.0, and reactions were performed in 96-well plates and GeneAmp 9700 thermal cyclers, using ABI Prism 7500 sequence detection system and ABI Prism 7500 SDS. Software version 1.0 software to detect and analyze fluorescence intensity. In this third step, all subjects, regardless of their diopter DNA, were identified for SNP genotypes. In the third step, the BICD1 gene was mainly focused, and the genetic effects of SNP rsl0771923, SNP rsll51029, and SNP rs7966276 in more than 3,000 subjects were analyzed in different genetic models. The gene frequencies of each SNP are shown in Table 1. Referring to Table 2, when the minor dual gene G of rsl0771923 has an additive effect (p = 〇.〇〇〇88, OR=1.22) or 0911-A51298-TW 15 201011107 rsll5H)29, the minor dual gene T is dominant. In the case of detrimental effect (d〇minant deleterious), the most relevant results can be obtained in two phenotypes (g jo as 斟 细 & -6D as myopia), while snp^96627=6 is more relevant to myopia than other The two SNPs come low. When the number of myopia is continuous and the number is analyzed, Λ3 s s s show meaningful results, as shown in Table 2. Figure 1 shows the relationship between the frequency of the SNp rsll51029 dual gene τ and the diopter, and the horizontal axis represents the diopter. Table 1, dual gene frequency and BICD1 gene typing analysis rsl0771923 TS115102Q rs7966276 diopter sample number MAF sample number MAF sample number MAF ^ -3D 1305 0.375 0wu 0.211 1215 0.040 -3D to -6 D 941 0.400 1148 0.228 953 0.027 ^ -6D 1027 0.423 1139 0.247 794 0.025 total 3273 0.397 3917 0.226 2962 0.032 MAF (minor allele frequency): secondary dual gene frequency table 2. Logistic regression analysis of binary features (normal / moderate myopia vs. high myopia) ________ _ genotype _____OR (p value) lSf (〇/〇) N (%) N (%) Total joint force display tile concealed ΑΑ tsI 0771923

2-3 D ^-6 D 5091338(32.9) \)/ \-/ 1 7 1447.1049. 6 5 \»7 V-^ ο 4 8214.7917. 02 !·22 1.30 1.30 (0.00088) (0.0024) (0.021)

Rsl 151029 AA AT TT

^ -3 D ^-6D 3 3 6 1 IX \—/ \7 5 4 84(5.70(6. \-y \ly 8 1 519(31.423(37. \—/ \J 7 ο 7 323·; £ 6· 10(664(5 !·22 1.30 1.21 (0.0017) (0.00088) (0.263)

Rs7966276 TT AT AA

2-3 D ^-6D \ϊ/' ο - 90(7.39(4.1 222.3)55.0)1 11(9275(9 4)3 .2(0 (00 94 〇·61 0.62 (0.0114) (0.0161)

0911-A51298-TW 16 201011107 Table 3. Analysis of diopter genotype-additive recessive P値βχ 100 Ρ値BxlOO P値BxlOO P値rsl0771923 0.0128 48.4 0.0032 29.2 0.0115 35.4 0.0230 rsl 151029 0.020 46.9 0.0060 28.8 0.0060 29.6 0.181 rs7966276 0.022 -125.1 0.0060 -62.7 0.0077 -173.8 0.260 Although the present invention has been disclosed in the above preferred embodiments, it is not intended to limit the invention, and any person skilled in the art without departing from the spirit of the invention In the scope of the invention, the scope of protection of the invention is defined by the scope of the appended claims.

Reference

0911-A51298-TW 17 201011107 [Simple description of the diagram] Figure 1 shows the relationship between the frequency of the rsl 151029 dual gene T and each diopter. [Main component symbol description] No 0

0911-A51298-TW 18

Claims (1)

201011107 VII. Patent application scope: 1. A method for determining whether a body is sensitive to myopia, comprising: obtaining a biological sample from the individual, and determining at least one single nucleotide polymorphism of the BICD1 gene in the biological sample. Sex (SNP), in which a dangerous genotype of the mononucleotide polymorphism is present, indicates that the individual is susceptible to myopia. 2. A method for determining whether a body is susceptible to myopia as described in claim 1 of the scope of the patent application, wherein the single nucleotide polymorphism is selected from the following 10 groups: SNPsrs7966276, rsll51029, rs2650122, and rsl0771923 . 3. A method for determining whether a body is susceptible to myopia as described in claim 1 of the patent application, wherein when the single nucleotide polymorphism is a dual gene G of SNP rsl0771923 or a dual gene T of SNP rsll51029, This individual is highly susceptible to myopia. 4. A method of determining whether a body is susceptible to myopia as described in claim 3, wherein the high sensitivity indicates a relative risk of at least 1.2 times greater than the reference. 5. A method of determining whether a body is susceptible to myopia as described in claim 3, wherein the high sensitivity indicates a relative risk of at least greater than 1.3 times. 6. A method for determining whether a body is susceptible to myopia as described in claim 1 of the patent application, wherein when the single nucleotide polymorphism is a dual gene A of SNP rs7966276, the individual is susceptible to myopia. Low susceptibility. 7. A method of determining whether a body is susceptible to myopia as described in claim 6 of the scope of the patent application, wherein the low sensitivity indicates a relative risk of at least 0.6 times greater than 0911-A5I298-TW 19 201011107. 8. A method of determining whether a body is susceptible to myopia as described in claim 1 of the scope of the patent application, wherein the individual is a mammal. 9. A method of determining whether a body is susceptible to myopia, as described in claim 1, wherein the biological sample comprises blood, amniotic fluid, cerebrospinal fluid, or tissue fluid from the skin, muscle, conjunctiva, placenta or gastrointestinal tract. 10. A method of screening for a substance that inhibits or treats myopia and/or myopia-related complications, comprising: ® contacting a test substance with a cell expressing a BICD1 gene, and screening a substance, as compared to a control group, Substances have the ability to regulate the expression of the BICD1 gene. 11. A method of screening for inhibition or treatment of myopia and/or myopia-related complications as described in claim 10, wherein the BICD1 gene comprises a single nucleotide polymorphic SNPs rs7966276, rsll51029, rs2650122, or rsl0771923. φ 12. A method for inhibiting or treating myopia and/or myopia-related complications as described in claim 10, wherein the substance comprises a compound, a small molecule drug, a saccharide, a nucleotide, a protein, Or peptide. 13. A method for assessing the response of a body to a myopic therapeutic agent, comprising determining a single nucleotide polymorphism of a BICD1 gene, wherein the genotype carrying the single nucleotide polymorphism indicates the individual There is a good response (positive reaction) to the myopia treatment agent. 14. Assessing the response of a body to a myopia treatment agent as described in claim 13, wherein the single nucleotide polymorphism of the BICD1 gene 0911-A51298-TW 20 201011107 may be selected from the group consisting of :SNPs rs7966276, rsll51029, rs2650122, and rsl0771923. 15. A kit for detecting myopia susceptibility comprising one or more reagents, a buffer, and an enzyme for detecting single nucleotide polymorphism of one or more BICD1 genes. 16. The kit for detecting myopia sensitivity according to claim 15, wherein the single nucleotide polymorphism of the BICD1 gene is selected from the group consisting of SNPs rs7966276, rsl 151029, rs2650122, and Rsl0771923. ❹ 17. The kit for detecting myopia sensitivity according to claim 15, wherein the reagent or the reagent comprises at least one contiguous nucleotide sequence, and the at least one single nucleotide comprising the BICD1 gene The nucleotide sequences of the type are complementary. 18. The kit for detecting myopia susceptibility as described in claim 15 of the patent application, further comprising at least one restriction enzyme. 19. The kit for detecting myopia susceptibility as described in claim 15 of the patent application, further comprising a fluorescent or chemiluminescent substance. ❹ 0911-A51298-TW 21