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  • Problem in merging 1000G and cases in Plink

    I have some problems in stating the imputation. I work on imputation in case-only design. My reference panel is build37 of 1000G (phase 3) in VCF format and a set of data including cases (in Plink format). before starting imputation in "Minimac3" prephasing with "shapeit" is necessary. "merging cases and controls(reference panel)" and "flip" them is necessary before prephasin.

    But I have some problems in the first steps. I converted the ref. panel from VCF to Plink and tried to merge them with cases. I have this Error:

    Warning: Multiple positions seen for variant 'rs201556956'.

    .

    .

    Warning: Multiple positions seen for variant 'rs200991502'.
    17838 markers loaded from CD_GermanyKielchr2_mod.bim.
    7047141 markers to be merged from ref_b37_ph3.bim.
    Of these, 7029359 are new, while 17782 are present in the base dataset.
    Error: 7932 variants with 3+ alleles present.
    * If you believe this is due to strand inconsistency, try --flip with
    merge.missnp.
    (Warning: if this seems to work, strand errors involving SNPs with A/T or C/G
    alleles probably remain in your data. If LD between nearby SNPs is high,
    --flip-scan should detect them.)
    * If you are dealing with genuine multiallelic variants, we recommend exporting
    that subset of the data to VCF (via e.g. '--recode vcf'), merging with
    another tool/script, and then importing the result; PLINK is not yet suited
    to handling them.

    Then I tried to remove them(but generally I do not want to remove them) and merge them but I have the other error:


    Error: 7916 variants with 3+ alleles present.
    * If you believe this is due to strand inconsistency, try --flip with
    merge1.missnp.
    (Warning: if this seems to work, strand errors involving SNPs with A/T or C/G
    alleles probably remain in your data. If LD between nearby SNPs is high,
    --flip-scan should detect them.)
    * If you are dealing with genuine multiallelic variants, we recommend exporting
    that subset of the data to VCF (via e.g. '--recode vcf'), merging with
    another tool/script, and then importing the result; PLINK is not yet suited
    to handling them.

    Now I would like to know what is the reason and in which file there is a problem as I have some errors which shows I have duplicate data! So I decided to check all the "multiple_position" SNP and "merge1.missnp" to explore if they are in the cases or in the reference panel.

    Could you give me some advice how I can solve this level to go to next step(prephasing)? Is there some algorithms to check or better view points? As I am new in Bioinformatics I guess maybe there are better ways.

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