Impact Of Ancestry Informative Markers On Autoimmune Diseases Association Study And Its Application In Analysis Of Population Stratification In Association Study

Objective (1)To detect whether Ancestry informative markers can confound result ofautoimmune diseases,including(Rheumatoid arthritis,RA),(Ankylosing spondylitis,AS),and Systemic lupus erythematosus SLE) association study.(2)To detect the effect of HanChinese population structureand on Genome-wide association studies.(3)To detect thedifference of Ancestry informative markers(AIMs) Allele frequencies between HanChinese Rheumatoid Arthritis casese and heath controls and among different regions ofHan Chinese.Methods We selected the association studies about the susceptibility gene of theautoimmune diseases,including RA,AS,SLE and Ancestry informative markers,whichshow large difference between the different populations,and long-range LD regionswhic h can co nfound the result of assoc iatio n study.Inq uesting the positio nsof the susceptibility gene of the RA,AS,SLE and the AIMs on the chromosome by(http://www.ncbi.nlm.nih.gov/) and (http://www.scandb.org/newinterface/index.html.).Finally,comparing the position between the susceptibility gene of the RA,AS,SLE andthe AIMs,long-range LD regions.（2） Principal components analysis (PCA) wasperformed at the individual level in EIGENSOFT version3.0, to analysis the populationstratification of Han Chinese,which including1846unrelated Han Chinese,928are RAcases samples,918are health controls.1846samples genetype on Illunima Human ominizhonghua. These samples represent Han Chinese populations residing in4administrativeregions of China.(3) Comparing allele frequencies of the AIMs between the RA casesand health controls,and among different regions of China via X2test.Results:(1)We finded1004AIMs and41long-range LD regions,which may confoundthe result of the assciation studies,and also find about100susceptibility gene of theautoimmune diseases(including RA,AS,SLE),and inquesting the positions of the AIMsand susceptibility gene,finally comparing the position between the AIMs,Long-range LDregions and the susceptibility gene.we cann’t find the AIMs and long range LD canconfoud the result of autoimmune diseases association study.(2) The1846Han Chinesesamples were studied via PCA with EIGENSOFT. The PCA was performed on the basisof247,739autosomal SNPs shared by all1846samples. The PCA result showing a verysubtle population stratification, The genome-wide x2infation factor which indicator ofthe infation of false-positive rates due to the presence of population substructure, λcalculated was1.093for the all the SNPs, indicating that the analysis has been well controlled for population stratification,the impact of population stratification onGenome-wide association studies is small. We aslo study the population stratificationabout four regions of China via PCA,including Shenyang,Beijing,Shanghai,Chengdouand the result show subtle population stratification between different populations.(3)Finally,we selected221AIMs genetype on Illunima Human omini zhonghua andcomparing the allele frequencies between RA cases and health controls and amongdifferent populations of Han Chinese, we found no AIMs showed statistically significantdifference between RA cases and health controls,and different regions of China.Conclusion(1)We didn’t find AIMs and long-range LD can confound the result of association studiesabout RA,AS,SLE by comparing the positions of the AIMs,long-range LD regions andthe susceptibility gene of the autoimmune diseases on the chromosome.(2)Han Chinese population showed very small population stratification,and the impact onthe association study is small.(3)221AIMs didn’t show statistically significant difference between RA cases and healthcontrols,and there was any AIMs showing statistically significant difference amongdifferent populations of Han Chinese.