{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T13:38:43Z","timestamp":1793367523168,"version":"4.5.0"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Beh\u00e7et disease (BD) is a polygenic, multifactorial, multisystem inflammatory condition with unknown etiology. Global distribution of BD is geographically structured, highest prevalence observed among East Asian, Middle Eastern, and Mediterranean populations. Although adaptive selection on a few BD susceptibility loci is speculated, a thorough evolutionary analysis on the genetic architecture of BD is lacking. We aimed to understand whether increased BD risk in the human populations with high prevalence is due to past selection on BD associated genes. We performed population genetics analyses with East Asian (high BD prevalence), European (low\/very low BD prevalence), and African (very low\/no BD prevalence) populations. Comparison of ancestral and derived alleles\u2019 frequencies versus their reported susceptible or protective effect on BD showed both derived and ancestral alleles are associated with increased BD risk. Variants showing higher risk to and more significant association with BD had smaller allele frequency differences, and showed less population differentiation compared to variants that showed smaller risk and less significant association with BD. Results suggest BD alleles are not unique to East Asians but are also found in other world populations at appreciable frequencies, and argue against selection favoring these variants only in populations with high BD prevalence. BD associated gene analyses showed similar evolutionary histories driven by neutral processes for many genes or balancing selection for HLA (Human Leukocyte Antigen) genes in all three populations studied. However, nucleotide diversity in several HLA region genes was much higher in East Asians suggesting selection for high nucleotide and haplotype diversity in East Asians. Recent selective sweep for genes involved in antigen recognition, peptide processing, immune and cellular differentiation regulation was observed only in East Asians. We conclude that the evolutionary processes shaping the genetic diversity in BD risk genes are diverse, and elucidating the underlying specific selection mechanisms is complex. Several of the genes examined in this study are risk factors (such as <jats:italic>ERAP1<\/jats:italic>, <jats:italic>IL23R<\/jats:italic>, <jats:italic>HLA-G<\/jats:italic>) for other inflammatory diseases. Thus, our conclusions are not only limited to BD but may have broader implications for other inflammatory diseases.<\/jats:p>","DOI":"10.3389\/fgene.2022.983646","type":"journal-article","created":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T04:49:49Z","timestamp":1664513389000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Diverse selection pressures shaping the genetic architecture of beh\u00e7et disease susceptibility"],"prefix":"10.3389","volume":"13","author":[{"given":"Efe","family":"Sezgin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif","family":"Kaplan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","year":"2015","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1534\/genetics.107.082198","article-title":"Testing for neutrality in samples with sequencing errors","volume":"179","author":"Achaz","year":"2008","journal-title":"Genetics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e286","DOI":"10.1371\/journal.pbio.0020286","article-title":"Population history and natural selection shape patterns of genetic variation in 132 genes","volume":"2","author":"Akey","year":"2004","journal-title":"PLoS Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1086\/421051","article-title":"Genetic signatures of strong recent positive selection at the lactase gene","volume":"74","author":"Bersaglieri","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1038\/nature04240","article-title":"Natural selection on protein-coding genes in the human genome","volume":"437","author":"Bustamante","year":"2005","journal-title":"Nature"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.1101\/gr.4326505","article-title":"Genomic regions exhibiting positive selection identified from dense genotype data","volume":"15","author":"Carlson","year":"2005","journal-title":"Genome Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"D1003","DOI":"10.1093\/nar\/gkx943","article-title":"PopHuman: The human population genomics browser","volume":"46","author":"Casillas","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"4135","DOI":"10.1007\/s10067-021-05688-6","article-title":"Adverse pregnancy outcomes in women with behcet's disease: Population-based registry linkage study in taiwan","volume":"40","author":"Chan","year":"2021","journal-title":"Clin. Rheumatol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: Rising to the challenge of larger and richer datasets","volume":"4","author":"Chang","year":"2015","journal-title":"Gigascience"},{"key":"B11","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1136\/heart.89.6.681","article-title":"Ethnic differences in cardiovascular disease","volume":"89","author":"Chaturvedi","year":"2003","journal-title":"Heart"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.1126\/science.1088821","article-title":"Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios","volume":"302","author":"Clark","year":"2003","journal-title":"Science"},{"key":"B13","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1016\/j.autrev.2011.10.022","article-title":"Genes, epigenetic regulation and environmental factors: Which is the most relevant in developing autoimmune diseases?","volume":"11","author":"Costenbader","year":"2012","journal-title":"Autoimmun. Rev."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2223","DOI":"10.2165\/11641370-000000000-00000","article-title":"Behcet's syndrome","volume":"72","author":"Dalvi","year":"2012","journal-title":"Drugs"},{"key":"B15","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1046\/j.1467-789x.2002.00065.x","article-title":"Asians are different from Caucasians and from each other in their body mass index\/body fat per cent relationship","volume":"3","author":"Deurenberg","year":"2002","journal-title":"Obes. Rev."},{"key":"B16","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1016\/j.tig.2005.08.007","article-title":"An evolutionary framework for common diseases: The ancestral-susceptibility model","volume":"21","author":"Di Rienzo","year":"2005","journal-title":"Trends Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1126\/science.1113722","article-title":"Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans","volume":"309","author":"Evans","year":"2005","journal-title":"Science"},{"key":"B18","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1126\/science.aag0776","article-title":"Detection of human adaptation during the past 2000 years","volume":"354","author":"Field","year":"2016","journal-title":"Science"},{"key":"B19","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1093\/genetics\/133.3.693","article-title":"Statistical tests of neutrality of mutations","volume":"133","author":"Fu","year":"1993","journal-title":"Genetics"},{"key":"B20","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1093\/genetics\/147.2.915","article-title":"Statistical tests of neutrality of mutations against population growth, hitchhiking and background selection","volume":"147","author":"Fu","year":"1997","journal-title":"Genetics"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1084\/jem.20082779","article-title":"Parasites represent a major selective force for interleukin genes and shape the genetic predisposition to autoimmune conditions","volume":"206","author":"Fumagalli","year":"2009","journal-title":"J. Exp. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1097\/bor.0000000000000003","article-title":"Genetics of behcet's disease: Lessons learned from genomewide association studies","volume":"26","author":"Gul","year":"2014","journal-title":"Curr. Opin. Rheumatol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1086\/338628","article-title":"Complex signatures of natural selection at the Duffy blood group locus","volume":"70","author":"Hamblin","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"B24","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.rdc.2013.02.010","article-title":"Behcet's syndrome","volume":"39","author":"Hatemi","year":"2013","journal-title":"Rheum. Dis. Clin. North Am."},{"key":"B25","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1111\/2041-210x.12808","article-title":"Soft sweeps and beyond: Understanding the patterns and probabilities of selection footprints under rapid adaptation","volume":"8","author":"Hermisson","year":"2017","journal-title":"Methods Ecol. Evol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"9362","DOI":"10.1073\/pnas.0903103106","article-title":"Potential etiologic and functional implications of genome-wide association loci for human diseases and traits","volume":"106","author":"Hindorff","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B27","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1093\/oxfordjournals.molbev.a040703","article-title":"A statistical test for detecting geographic subdivision","volume":"9","author":"Hudson","year":"","journal-title":"Mol. Biol. Evol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1093\/genetics\/132.2.583","article-title":"Estimation of levels of gene flow from DNA sequence data","volume":"132","author":"Hudson","year":"","journal-title":"Genetics"},{"key":"B29","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1093\/molbev\/msg092","article-title":"A genome scan to detect candidate regions influenced by local natural selection in human populations","volume":"20","author":"Kayser","year":"2003","journal-title":"Mol. Biol. Evol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1136\/bjo.2007.124875","article-title":"Behcet's disease: Global epidemiology of an old Silk Road disease","volume":"91","author":"Keino","year":"2007","journal-title":"Br. J. Ophthalmol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1093\/genetics\/146.3.1197","article-title":"A test of neutrality based on interlocus associations","volume":"146","author":"Kelly","year":"1997","journal-title":"Genetics"},{"key":"B32","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/ng.2520","article-title":"Genome-wide association analysis identifies new susceptibility loci for Behcet's disease and epistasis between HLA-B*51 and ERAP1","volume":"45","author":"Kirino","year":"","journal-title":"Nat. Genet."},{"key":"B33","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1038\/nrrheum.2015.41","article-title":"Genetic architectures of seropositive and seronegative rheumatic diseases","volume":"11","author":"Kirino","year":"2015","journal-title":"Nat. Rev. Rheumatol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"8134","DOI":"10.1073\/pnas.1306352110","article-title":"Targeted resequencing implicates the familial Mediterranean fever gene MEFV and the toll-like receptor 4 gene TLR4 in Behcet disease","volume":"110","author":"Kirino","year":"","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B35","doi-asserted-by":"publisher","first-page":"57","DOI":"10.32614\/RJ-2012-014","article-title":"Rfit: Rank-based estimation for linear models","volume":"4","author":"Kloke","year":"2012","journal-title":"R J."},{"key":"B36","doi-asserted-by":"publisher","first-page":"945262","DOI":"10.1155\/2015\/945262","article-title":"Behcet's disease: Is there geographical variation? A review far from the Silk Road","volume":"2015","author":"Leonardo","year":"2015","journal-title":"Int. J. Rheumatol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1111\/1756-185x.12369","article-title":"IL10 low-frequency variants in Behcet's disease patients","volume":"20","author":"Matos","year":"2017","journal-title":"Int. J. Rheum. Dis."},{"key":"B38","doi-asserted-by":"publisher","first-page":"713052","DOI":"10.3389\/fmed.2021.713052","article-title":"Pathogenesis of behcet's syndrome: Genetic, environmental and immunological factors","volume":"8","author":"Mattioli","year":"2021","journal-title":"Front. Med. (Lausanne)"},{"key":"B39","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1038\/351652a0","article-title":"Adaptive protein evolution at the Adh locus in Drosophila","volume":"351","author":"McDonald","year":"1991","journal-title":"Nature"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1720","DOI":"10.1126\/science.1116815","article-title":"Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens","volume":"309","author":"Mekel-Bobrov","year":"2005","journal-title":"Science"},{"key":"B41","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1023\/a:1007529206050","article-title":"Food intake patterns and 25-year mortality from coronary heart disease: Cross-cultural correlations in the seven countries study. The seven countries study research group","volume":"15","author":"Menotti","year":"1999","journal-title":"Eur. J. Epidemiol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/978-1-60761-175-2_7","article-title":"PANTHER pathway: An ontology-based pathway database coupled with data analysis tools","volume":"563","author":"Mi","year":"2009","journal-title":"Methods Mol. Biol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/ng.733","article-title":"Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease","volume":"43","author":"Momozawa","year":"2011","journal-title":"Nat. Genet."},{"key":"B44","doi-asserted-by":"crossref","DOI":"10.7312\/nei-92038","volume-title":"Molecular evolutionary genetics","author":"Nei","year":"1987"},{"key":"B45","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1159\/000520696","article-title":"Behcet's disease: An in-depth review about pathogenesis, gastrointestinal manifestations, and management","volume":"6","author":"Nguyen","year":"2021","journal-title":"Inflamm. Intest. Dis."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e170","DOI":"10.1371\/journal.pbio.0030170","article-title":"A scan for positively selected genes in the genomes of humans and chimpanzees","volume":"3","author":"Nielsen","year":"2005","journal-title":"PLoS Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1001\/archopht.1982.01030040433013","article-title":"Close association of HLA-Bw51 with Behcet's disease","volume":"100","author":"Ohno","year":"1982","journal-title":"Arch. Ophthalmol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1097\/bor.0000000000000189","article-title":"Endoplasmic reticulum-associated amino-peptidase 1 and rheumatic disease: Genetics","volume":"27","author":"Ombrello","year":"2015","journal-title":"Curr. Opin. Rheumatol."},{"key":"B49","first-page":"S123","article-title":"The origin of behcet's disease geoepidemiology: Possible role of a dual microbial-driven genetic selection","volume":"32","author":"Piga","year":"2014","journal-title":"Clin. Exp. Rheumatol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","article-title":"Plink: A tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"B51","doi-asserted-by":"publisher","first-page":"2092","DOI":"10.1093\/oxfordjournals.molbev.a004034","article-title":"Statistical properties of new neutrality tests against population growth","volume":"19","author":"Ramos-Onsins","year":"2002","journal-title":"Mol. Biol. Evol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1093\/oxfordjournals.molbev.a025634","article-title":"Excess amino acid polymorphism in mitochondrial DNA: Contrasts among genes from Drosophila, mice, and humans","volume":"13","author":"Rand","year":"1996","journal-title":"Mol. Biol. Evol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1038\/ng.625","article-title":"Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behcet's disease","volume":"42","author":"Remmers","year":"2010","journal-title":"Nat. Genet."},{"key":"B54","doi-asserted-by":"publisher","first-page":"91","DOI":"10.2478\/rir-2021-0013","article-title":"A Darwinian view of Beh\u00e7et's disease","volume":"2","author":"Rhodri","year":"2021","journal-title":"Rheumatology Immunol. Res."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1038\/ng.3401","article-title":"Population genetic differentiation of height and body mass index across Europe","volume":"47","author":"Robinson","year":"2015","journal-title":"Nat. Genet."},{"key":"B56","doi-asserted-by":"publisher","first-page":"3299","DOI":"10.1093\/molbev\/msx248","article-title":"DnaSP 6: DNA sequence polymorphism analysis of large data sets","volume":"34","author":"Rozas","year":"2017","journal-title":"Mol. Biol. Evol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1136\/ard.2007.080283","article-title":"The IL23R Arg381Gln non-synonymous polymorphism confers susceptibility to ankylosing spondylitis","volume":"67","author":"Rueda","year":"2008","journal-title":"Ann. Rheum. Dis."},{"key":"B58","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1038\/nature01140","article-title":"Detecting recent positive selection in the human genome from haplotype structure","volume":"419","author":"Sabeti","year":"2002","journal-title":"Nature"},{"key":"B59","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1038\/nature06250","article-title":"Genome-wide detection and characterization of positive selection in human populations","volume":"449","author":"Sabeti","year":"2007","journal-title":"Nature"},{"key":"B60","first-page":"S60","article-title":"Tracing behcet's disease origins along the Silk Road: An anthropological evolutionary genetics perspective","volume":"33","author":"Sazzini","year":"2015","journal-title":"Clin. Exp. Rheumatol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"B62","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1093\/nar\/29.1.308","article-title":"dbSNP: the NCBI database of genetic variation","volume":"29","author":"Sherry","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1038\/4151022a","article-title":"Adaptive protein evolution in Drosophila","volume":"415","author":"Smith","year":"2002","journal-title":"Nature"},{"key":"B64","doi-asserted-by":"publisher","first-page":"91","DOI":"10.2478\/rir-2021-0013","article-title":"A Darwinian view of Beh\u00e7et's disease","volume":"2","author":"Smith","year":"2021","journal-title":"Rheumatology Immunol. Res."},{"key":"B65","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1093\/molbev\/msh252","article-title":"Disentangling the effects of demography and selection in human history","volume":"22","author":"Stajich","year":"2005","journal-title":"Mol. Biol. Evol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/ng1508","article-title":"A common inversion under selection in Europeans","volume":"37","author":"Stefansson","year":"2005","journal-title":"Nat. Genet."},{"key":"B67","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1093\/molbev\/msq249","article-title":"Estimation of the neutrality index","volume":"28","author":"Stoletzki","year":"2011","journal-title":"Mol. Biol. Evol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1800","DOI":"10.1093\/molbev\/msh192","article-title":"Genome scans of DNA variability in humans reveal evidence for selective sweeps outside of Africa","volume":"21","author":"Storz","year":"2004","journal-title":"Mol. Biol. Evol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1111\/brv.12165","article-title":"Evolutionary perspectives on human height variation","volume":"91","author":"Stulp","year":"2016","journal-title":"Biol. Rev. Camb Philos. Soc."},{"key":"B70","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1038\/s41597-019-0043-4","article-title":"Atlas of RNA sequencing profiles for normal human tissues","volume":"6","author":"Suntsova","year":"2019","journal-title":"Sci. Data"},{"key":"B71","doi-asserted-by":"publisher","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","article-title":"The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"B72","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1093\/genetics\/105.2.437","article-title":"Evolutionary relationship of DNA sequences in finite populations","volume":"105","author":"Tajima","year":"1983","journal-title":"Genetics"},{"key":"B73","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1093\/genetics\/123.3.585","article-title":"Statistical method for testing the neutral mutation hypothesis by DNA polymorphism","volume":"123","author":"Tajima","year":"1989","journal-title":"Genetics"},{"key":"B74","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.jaut.2015.08.013","article-title":"The immunogenetics of behcet's disease: A comprehensive review","volume":"64","author":"Takeuchi","year":"2015","journal-title":"J. Autoimmun."},{"key":"B75","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/ng.2827","article-title":"A large-scale screen for coding variants predisposing to psoriasis","volume":"46","author":"Tang","year":"2014","journal-title":"Nat. Genet."},{"key":"B76","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v014.i07","article-title":"Rank-based analysis of linear models using R","volume":"14","author":"Terpstra","year":"2005","journal-title":"J. Stat. Softw."},{"key":"B77","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1086\/426406","article-title":"CYP3A variation and the evolution of salt-sensitivity variants","volume":"75","author":"Thompson","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"B78","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1590\/s1677-5538.ibju.2014.0595","article-title":"Male fertility potential alteration in rheumatic diseases: A systematic review","volume":"42","author":"Tiseo","year":"2016","journal-title":"Int. Braz J. Urol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1126\/science.1061573","article-title":"Haplotype diversity and linkage disequilibrium at human G6PD: Recent origin of alleles that confer malarial resistance","volume":"293","author":"Tishkoff","year":"2001","journal-title":"Science"},{"key":"B80","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1086\/428784","article-title":"Population genetics of CAPN10 and GPR35: Implications for the evolution of type 2 diabetes variants","volume":"76","author":"Vander Molen","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"B81","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1034\/j.1399-0039.1999.540301.x","article-title":"Behcet's disease, the Silk Road and HLA-B51: Historical and geographical perspectives","volume":"54","author":"Verity","year":"1999","journal-title":"Tissue Antigens"},{"key":"B82","doi-asserted-by":"publisher","first-page":"e72","DOI":"10.1371\/journal.pbio.0040072","article-title":"A map of recent positive selection in the human genome","volume":"4","author":"Voight","year":"2006","journal-title":"PLoS Biol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/0040-5809(75)90020-9","article-title":"On the number of segregating sites in genetical models without recombination","volume":"7","author":"Watterson","year":"1975","journal-title":"Theor. Popul. Biol."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.983646\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T04:49:54Z","timestamp":1664513394000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.983646\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,30]]},"references-count":82,"alternative-id":["10.3389\/fgene.2022.983646"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.983646","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,30]]},"article-number":"983646"}}