Editing Single-nucleotide polymorphism (section)

=== Clinical research ===

==== Genome-wide association study (GWAS) ====
One of the main contributions of SNPs in clinical research is genome-wide association study (GWAS).<ref name="auto">{{Cite journal|last1=Visscher|first1=Peter M.|last2=Wray|first2=Naomi R.|last3=Zhang|first3=Qian|last4=Sklar|first4=Pamela|last5=McCarthy|first5=Mark I.|last6=Brown|first6=Matthew A.|last7=Yang|first7=Jian|date=July 2017|title=10 Years of GWAS Discovery: Biology, Function, and Translation|url=|journal=The American Journal of Human Genetics|volume=101|issue=1|pages=5–22|doi=10.1016/j.ajhg.2017.06.005|pmid=28686856|pmc=5501872|issn=0002-9297}}</ref> Genome-wide genetic data can be generated by multiple technologies, including SNP array and whole genome sequencing. GWAS has been commonly used in identifying SNPs associated with diseases or clinical phenotypes or traits. Since GWAS is a genome-wide assessment, a large sample site is required to obtain sufficient statistical power to detect all possible associations. Some SNPs have relatively small effect on diseases or clinical phenotypes or traits. To estimate study power, the genetic model for disease needs to be considered, such as dominant, recessive, or additive effects. Due to genetic heterogeneity, GWAS analysis must be adjusted for race.

==== Candidate gene association study ====
Candidate gene association study is commonly used in genetic study before the invention of high throughput genotyping or sequencing technologies.<ref>{{Cite journal|last1=Dong|first1=Linda M.|last2=Potter|first2=John D.|last3=White|first3=Emily|last4=Ulrich|first4=Cornelia M.|last5=Cardon|first5=Lon R.|last6=Peters|first6=Ulrike|date=2008-05-28|title=Genetic Susceptibility to Cancer|url=|journal=JAMA|volume=299|issue=20|pages=2423–2436|doi=10.1001/jama.299.20.2423|pmid=18505952|pmc=2772197|issn=0098-7484}}</ref> Candidate gene association study is to investigate limited number of pre-specified SNPs for association with diseases or clinical phenotypes or traits. So this is a hypothesis driven approach. Since only a limited number of SNPs are tested, a relatively small sample size is sufficient to detect the association. Candidate gene association approach is also commonly used to confirm findings from GWAS in independent samples.

==== Homozygosity mapping in disease ====
Genome-wide SNP data can be used for homozygosity mapping.<ref>{{Cite journal|last=Alkuraya|first=Fowzan S.|date=April 2010|title=Homozygosity mapping: One more tool in the clinical geneticist's toolbox|journal=Genetics in Medicine|volume=12|issue=4|pages=236–239|doi=10.1097/gim.0b013e3181ceb95d|pmid=20134328|s2cid=10789932|issn=1098-3600|doi-access=free}}</ref> Homozygosity mapping is a method used to identify homozygous autosomal recessive loci, which can be a powerful tool to map genomic regions or genes that are involved in disease pathogenesis.

==== Methylation patterns ====
[[File:Associations between SNPs, methylation patterns and gene expression.png|thumb|Associations between SNPs, methylation patterns and gene expression of biological traits]]
Recently, preliminary results reported SNPs as important components of the epigenetic program in organisms.<ref>{{Cite journal |last1=Vohra |first1=Manik |last2=Sharma |first2=Anu Radha |last3=Prabhu B |first3=Navya |last4=Rai |first4=Padmalatha S. |date=2020 |title=SNPs in Sites for DNA Methylation, Transcription Factor Binding, and miRNA Targets Leading to Allele-Specific Gene Expression and Contributing to Complex Disease Risk: A Systematic Review |journal=Public Health Genomics |volume=23 |issue=5–6 |pages=155–170 |doi=10.1159/000510253 |pmid=32966991 |s2cid=221886624 |issn=1662-4246|doi-access=free }}</ref><ref>{{Cite journal |last1=Wang |first1=Jing |last2=Ma |first2=Xiaoqin |last3=Zhang |first3=Qi |last4=Chen |first4=Yinghui |last5=Wu |first5=Dan |last6=Zhao |first6=Pengjun |last7=Yu |first7=Yu |date=2021 |title=The Interaction Analysis of SNP Variants and DNA Methylation Identifies Novel Methylated Pathogenesis Genes in Congenital Heart Diseases |journal=Frontiers in Cell and Developmental Biology |volume=9 |page=665514 |doi=10.3389/fcell.2021.665514 |issn=2296-634X |pmc=8143053 |pmid=34041244|doi-access=free }}</ref> Moreover, cosmopolitan studies in European and South Asiatic populations have revealed the influence of SNPs in the methylation of specific CpG sites.<ref name=":0">{{Cite journal |last1=Hawe |first1=Johann S. |last2=Wilson |first2=Rory |last3=Schmid |first3=Katharina T. |last4=Zhou |first4=Li |last5=Lakshmanan |first5=Lakshmi Narayanan |last6=Lehne |first6=Benjamin C. |last7=Kühnel |first7=Brigitte |last8=Scott |first8=William R. |last9=Wielscher |first9=Matthias |last10=Yew |first10=Yik Weng |last11=Baumbach |first11=Clemens |last12=Lee |first12=Dominic P. |last13=Marouli |first13=Eirini |last14=Bernard |first14=Manon |last15=Pfeiffer |first15=Liliane |date=January 2022 |title=Genetic variation influencing DNA methylation provides insights into molecular mechanisms regulating genomic function |journal=Nature Genetics |language=en |volume=54 |issue=1 |pages=18–29 |doi=10.1038/s41588-021-00969-x |pmid=34980917 |s2cid=256821844 |issn=1546-1718|pmc=7617265 }}</ref> In addition, meQTL enrichment analysis using GWAS database, demonstrated that those associations are important toward the prediction of biological traits.<ref name=":0" /><ref>{{Cite journal |last1=Perzel Mandell |first1=Kira A. |last2=Eagles |first2=Nicholas J. |last3=Wilton |first3=Richard |last4=Price |first4=Amanda J. |last5=Semick |first5=Stephen A. |last6=Collado-Torres |first6=Leonardo |last7=Ulrich |first7=William S. |last8=Tao |first8=Ran |last9=Han |first9=Shizhong |last10=Szalay |first10=Alexander S. |last11=Hyde |first11=Thomas M. |last12=Kleinman |first12=Joel E. |last13=Weinberger |first13=Daniel R. |last14=Jaffe |first14=Andrew E. |date=2021-09-02 |title=Genome-wide sequencing-based identification of methylation quantitative trait loci and their role in schizophrenia risk |journal=Nature Communications |language=en |volume=12 |issue=1 |pages=5251 |doi=10.1038/s41467-021-25517-3 |issn=2041-1723 |pmc=8413445 |pmid=34475392|bibcode=2021NatCo..12.5251P }}</ref><ref>{{Cite journal |last1=Hoffmann |first1=Anke |last2=Ziller |first2=Michael |last3=Spengler |first3=Dietmar |date=December 2016 |title=The Future is The Past: Methylation QTLs in Schizophrenia |journal=Genes |language=en |volume=7 |issue=12 |pages=104 |doi=10.3390/genes7120104 |issn=2073-4425 |pmc=5192480 |pmid=27886132|doi-access=free }}</ref>