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Genetic and Molecular Epidemiology (Modern epidemiology Chap. 28)

Shuntaro Sato
January 27, 2020

Genetic and Molecular Epidemiology (Modern epidemiology Chap. 28)

Modern epidemiology読書会
今回の動画は「Chap.28 Genetic and Molecular Epidemiology」です.
遺伝疫学・分子疫学について勉強していきます.
バイオマーカーの妥当性・Genome-wide association studiesの基本的な部分.遺伝x遺伝,遺伝x環境要因の相互作用をどのように評価していくのか触れています.

Shuntaro Sato

January 27, 2020
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  1. Chapter 28
    Genetic and Molecular Epidemiology
    Muin J. Khoury, Robert Millikan, and Marta Gwinn
    Chuntaro (@Shuntarooo3)
    1
    Modern Epidemiology

    View full-size slide

  2. Genome? Gene? Omic
    2
    ਫౡ-ੁ໺७ࢠʢஶʣɾαΩϚΠίʢ࡞ըʣʢ2018ʣʰϚϯΨͰΘ͔Δ ήϊϜҩֶʱ༽౔ࣾɹ
    Λࢀߟʹ࡞੒
    ճ
    Λ 䎠 ࣏འ
    ڵ
    ↴ɾ
    ੨ɺ
    ᮊɾ


    ࡉ๔
    ֩ છ৭ମ
    %/"
    Ҩ఻ࢠ"
    Ҩ


    #
    %/"
    N3/"
    λϯύΫ࣭
    ήϊϜʢHFOPNFʣ
    ͋Δੜ෺͕΋ͭછ৭ମதʹ͋Δ
    ͢΂ͯͷ%/"഑ྻ৘ใͷ͜ͱ
    ʢશҨ఻৘ใʣ
    Ҩ఻ࢠʢHFOFʣ
    %/"ͷҰ෦Ͱɼʮ͜ͷ഑ྻʹ͠
    ͕ͨͬͯλϯύΫ࣭Λ࡞Εʯͱ໋
    ྩ͍ͯ͠Δ෦෼ͷ͜ͱ
    (FOPNJDT
    1SPUFPNJDT w 5SBOTDSJQUPNJDT
    w .FUBCPOPNJDT
    w /VUSJHFOPNJDT
    w 1IBSNBDPHFOPNJDT
    w 5PYJDPHFOPNJDT
    0NJD
    ͞·͟·ͳ໢ཏతੜମ෼ࢠΛ
    ·ͱΊͨ஌ࣝɾू߹ͷ͜ͱ

    View full-size slide

  3. Genetic and Molecular Epidemiology
    3
    &YQPTVSFT
    4VTDFQUJCJMJUZ
    0VUDPNFT
    #JPMPHJDNBSLFST
    w ײછ঱Ӹֶɿ߅ମՁ
    w ৺݂؅࣬ױӸֶɿ݂தࢷ࣭
    w ؀ڥӸֶɿಟૉͷ݂தೱ౓
    .PMFDVMBSFQJEFNJPMPHZʢ෼ࢠӸֶʣ (FOFUJDFQJEFNJPMPHZʢҨ఻Ӹֶʣ
    (FOFUJD
    GBDUPST
    0VUDPNFT
    Wellcome Trust Case Control Consortium. (2007). Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared
    controls. Nature, 447(7145), 661.
    (FOF %JTFBTF
    %JTFBTF
    (FOF
    (FOF
    º
    (FOF
    &OWJSPONFOU
    º %JTFBTF

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  4. Overview
    4
    (FOF %JTFBTF
    %JTFBTF
    (FOF
    (FOF
    º
    (FOF
    &OWJSPONFOU
    º %JTFBTF
    "OBMZUJDBOENFUIPEPMPHJDBMJTTVFT
    &YBNQMF
    w େ௎͕Μ
    w Ԍ঱ੑେ௎Ԍ
    %POPUDPWFSUSBEJUJPOBMHFOFUJDBOBMZTFT
    w Ոܥ෼ੳ
    w ࿈࠯ղੳ
    w Ϛοϐϯά

    View full-size slide

  5. MULTIDISCIPLINARY APPROACHES TO THE EVALUATION OF
    BIOMARKERS (p. 566)
    5
    "OBMZUJDWBMJEJUZʢ෼ੳతଥ౰ੑʣ
    ͲͷΑ͏ͳόΠΦϚʔΧʔͰ͋ͬͯ΋ଥ౰ੑͷධՁ͸ඞཁ
    $MJOJDBMWBMJEJUZʢྟচతଥ౰ੑʣ
    $MJOJDBMVUJMJUZʢྟচత༗༻ੑʣ

    View full-size slide

  6. ANALYTIC VALIDITY (p. 566)
    6
    "OBMZUJDWBMJEJUZ
    ʢ෼ੳతଥ౰ੑʣ
    "DDVSBDZ
    ʢਖ਼֬ੑʣ

    Biomarker
    Test Present Absent
    + A B
    - C D
    =
    A
    A + C
    =
    D
    B + D
    "OBMZUJDTFOTJUJWJUZ
    ʢײ౓ʣ
    "OBMZUJDTQFDJpDJUZ
    ʢಛҟ౓ʣ
    ෼ੳతଥ౰ੑ͸ɼαϯϓϧͷछྨɼॲཧɼอଘ͓ΑͼΞοηΠͷଥ౰ੑʹґଘ͢Δ

    View full-size slide

  7. CLINICAL VALIDITY (p. 566)
    7
    ෼ੳతଥ౰ੑΛ্ཱ֬ͨ͠Ͱɼ
    ࣍͸ྟচతଥ౰ੑΛྟচ͓ΑͼӸֶݚڀͰධՁ͢Δඞཁ͕͋Δ
    Clinical Outcome
    Biomarker Present Absent
    + A B
    - C D
    =
    A
    A + C
    =
    D
    B + D
    $MJOJDBMTFOTJUJWJUZ
    ʢײ౓ʣ
    $MJOJDBMTQFDJpDJUZ
    ʢಛҟ౓ʣ
    =
    A
    A + B
    =
    D
    C + D
    1PTJUJWFQSFEJDUJWFWBMVF
    ʢཅੑదத཰ʣ
    /FHBUJWFQSFEJDUJWFWBMVF
    ʢӄੑదத཰ʣ
    ࣬ױ͋Γͷݸମʹରͯ͠
    ʢਖ਼͘͠ʣཅੑͱ਍அ͢Δ֬཰
    ࣬ױͳ͠ͷݸମʹରͯ͠
    ʢਖ਼͘͠ʣӄੑͱ਍அ͢Δ֬཰
    ཅੑͱ਍அ͞Εͨݸମʹ͓͍ͯ
    ਅʹ࣬ױ͕ଘࡏ͢Δ֬཰
    ӄੑͱ਍அ͞Εͨݸମʹ͓͍ͯ
    ਅʹ࣬ױ͕ଘࡏ͠ͳ͍֬཰

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  8. CLINICAL UTILITY (p. 567)
    8
    ྟচత༗༻ੑͱ͸ɼݕࠪʹΑΓΞ΢τΧϜ͕ྑ͘ͳΔ֬཰Λࣔ͢
    #VSLFFUBM

    Outcome
    Intervention Sick Not
    1 A B
    2 C D
    όΠΦϚʔΧʔ͕ཅੑͷݸମͷྟচత༗༻ੑධՁ
    ͜ͷද͸ɼόΠΦϚʔΧʔཅੑͷݸମʹରͯ͠ɼ
    ϥϯμϜʹ࣏ྍΛׂΓ౰ͯɼ࣏ྍͷޮՌΛධՁ͍ͯ͠Δ
    3$5ˠ
    όΠΦϚʔΧʔͷྟচత༗༻ੑͷධՁʹͳ͍ͬͯΔʁ
    ?

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  9. ETHICAL, LEGAL, AND SOCIAL ISSUES (p. 567)
    9
    όΠΦϚʔΧʔʢಛʹҨ఻৘ใʣΛ࢖༻͢Δݚڀ͸ɼͨ͘͞Μͷ
    FUIJDBMʢྙཧతʣ MFHBMʢ๏తʣ TPDJBMʢࣾձతʣͷJTTVFʢ՝୊ʣ
    E L S I
    w ΠϯϑΥʔϜυɾίϯηϯτ
    w ඃݧऀͷืू
    w ݚڀ݁Ռʹؔ͢Δ৘ใͷ։ࣔ
    w ݸਓ΍ूஂʹର͢ΔࠩผͷՄೳੑ

    View full-size slide

  10. CONVENTIONAL EPIDEMIOLOGIC STUDIES (p. 568)
    10
    w $BTFDPOUSPMTUVEJFT
    w $PIPSUTUVEJFT
    w $SPTTTFDUJPOBMTUVEJFT

    View full-size slide

  11. AlleleɾGenotype
    11
    છ৭ମ
    A - T
    T - A
    G - C
    C - G
    T - A
    ߏ଄Λ֦େ
    Ԙج഑ྻ
    %/"
    ˢ૬ิ࠯഑ྻ
    A A
    A A
    A A
    A a
    ෕༝དྷ ฼༝དྷ
    w ԘجͷόϦΤʔγϣϯΛΞϦϧʢBMMFMFʣ
    ͱ͍͏
    w ΞϦϧͷ૊Έ߹Θͤ
    ʮ""PS"BPSBBʯΛδΣϊλΠϓ
    ʢHFOPUZQFʣͱ͍͏

    View full-size slide

  12. SNV (Single Nucleotide Variant)
    12
    *% MPDVT MPDVT MPDVT MPDVT MPDVT
    "" "" "" "" ""
    "" "" "( "" ""
    "" "" (( "" ""

    ௕͞ͷԘجΛ࠲ҐʢMPDVTʣͱ͢Δ
    େ൒͸ಉҰ
    w ͱ͖Ͳ͖ҟͳΔΞϦϧΛؚΉมҟʢόϦΞϯτɼWBSJBOUʣ͕͋Δ
    w ԘجͷόϦΞϯτ͸4/7ʢ4JOHMF/VDMFPUJEF7BSJBOUʣ

    View full-size slide

  13. SNPɾMAF
    13
    δΣϊλΠϓ "" "B BB 5PUBM
    /
    ͋Δूஂʢ໊ʣͷ͋Δ4/7Λߟ͑Δ
    ΞϦϧ " B 5PUBM
    /
    ස౓




    º
    º

    ϚΠφʔΞϦϧස౓
    ʢ."'NJOPSBMMFMF
    GSFRVFODZʣ
    ස౓ͷগͳ͍ΞϦϧ
    4/1ʢҰԘجଟܕʣ."'㱢΍ͷ4/7ͷ͜ͱ

    View full-size slide

  14. CASE-CONTROL STUDIES (1) (p. 568)
    14
    Ҩ఻ࢠϚʔΧʔ͸ײडੑҼࢠͱͯ҆͠ఆ͍ͯ͠ΔͨΊɼ
    DBTFDPOUSPMTUVEJFTʹద͍ͯ͠Δ
    3FDBMMCJBT͸গͳ͍
    4VTDFQUJCJMJUZʢײडੑʣͱ͸ʁ
    Ҩ఻ੑ࣬ױ
    ୯ҰҨ఻ࢠ࣬ױ
    ଟҨ఻ੑ࣬ױʢ͋Γ;Εͨ࣬ױɼෳࡶ࣬ױɼDPNNPOEJTFBTFʣ
    ͭͷ࠲ҐʹΑܾͬͯఆతʹӨڹ͞ΕΔ
    খ͍͞د༩౓Λ΋ͬͨଟ͘ͷҨ఻తཁҼʹΑͬͯදݱܕ͕ܾఆ͞ΕΔ
    ײडੑҼࢠʢTVTDFQUJCJMJUZGBDUPSʣ
    w $POUSPM܈ʹରͯ͠$BTF܈ͰόϦΞϯτͷස౓͕༗ҙʹߴ͍͕ɼ
    Ұൠͷ݈ৗਓ΋͠͹͠͹ͦͷόϦΞϯτΛ༗͢Δ
    w $BTF܈Ͱ͋ͬͯ΋όϦΞϯτ͕ͳ͍ݸମ΋͋ΓಘΔ

    View full-size slide

  15. CASE-CONTROL STUDIES (2) (p. 568)
    15
    ͭͷόϦΞϯτͱ࣬ױͱͷؔ࿈͚ͩͰ͸ͳ͘ɼ
    ଞͷόϦΞϯτ΍ཁҼͱڞʹ࣬ױͱͷؔ࿈Λ୳ࡧͰ͖Δ
    w (FOFHFOFJOUFSBDUJPO
    w (FOFFOWJSPONFOUJOUFSBDUJPO
    ·ΕͳΤϯυϙΠϯτʢ3BSFEJTFBTFʣʹద͍ͯ͠Δ

    View full-size slide

  16. CASE-CONTROL STUDIES (3) (p. 568)
    16
    0VUDPNF
    :

    $PWBSJBUF
    &

    4/1
    (

    4/1
    (

    ʜ
    4/1K
    (





    w ήϊϜϫΠυؔ࿈ղੳʢ(8"4HFOPNFXJEFBTTPDJBUJPOTUVEZʣ
    w σβΠϯ͸έʔεɾίϯτϩʔϧݚڀ
    w ֤4/1ͱΞ΢τΧϜʢ஋ܗ࣭ʣͱͷؔ࿈Λݕ౼͢ΔϞσϧ
    w 4/1ͷ਺͚ͩݕఆΛ܁Γฦ͢ 4/1਺͸਺ेສʙ਺ઍສ

    View full-size slide

  17. COHORT STUDIES (p. 568)
    17
    ͋Γ;Εͨ࣬ױͱؔ࿈͢ΔҨ఻ࢠΛൃݟ͢ΔͨΊʹ໾ཱͭ
    w ॎஅతͳඇৗʹେن໛ͳूஂ
    w όΠΦόϯΫͷཱ֬
    Study Sample size Population Study Objectives
    Decode
    Genetics
    > 100,000 Iceland
    • ͋Γ;Εͨ࣬ױͷݪҼͱͳΔҨ఻ࢠͷಉఆ
    • ৽ༀͷ։ൃ౳
    UK Biobank 500,000
    Population sample of
    persons aged 45-69 y
    • Ҩ఻ࢠɼ؀ڥɼੜ׆ελΠϧͷ໾ׂ
    • Medical recordͱϦϯΫ
    CartaGene
    (Quebec)
    > 60,000
    Population sample of
    persons aged 25-74 y
    • Ҩ఻ࢠɼ؀ڥɼੜ׆ελΠϧɼ
    Medical recordͱϦϯΫ
    Estonia Genome
    Project
    > 1,000,000 Estonian population
    • ͋Γ;Εͨ࣬ױͷݪҼͱͳΔҨ఻ࢠͷಉఆ
    • Medical recordͱϦϯΫ
    GenomeEUTwin
    ʙ800,000
    twin pairs
    Twin cohorts from 7
    European countries +
    Australia
    • Ҩ఻ࢠɼ؀ڥɼੜ׆ελΠϧͷ໾ׂ
    ॊೈʹෳࡶͳϝΧχζϜɾԾઆ
    ʹରԠͰ͖Δ

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  18. CROSS-SECTIONAL STUDIES (p. 569)
    18
    ௐࠪ࣌఺ʹ͓͚Δ࣬ױͷ༗ප཰΍ͦͷ࣬ױʹؔ࿈͢ΔҨ఻ࢠΛ୳ࡧͰ͖Δ

    View full-size slide

  19. METHODOLOGIC ISSUES CONFOUNDING (p. 570)
    19
    ڵຯͷ͋ΔόϦΞϯτ ࣬ױ
    3BDFFUIOJDJUZ
    ʢਓछຽ଒ੑʣ
    ަབྷҼࢠ
    ަབྷҼࢠͷௐ੔ํ๏
    -PHJTUJDSFHSFTTJPONPEFM
    :ˡ4/1ڞมྔɹ㱺ɹ4/1ʹ͍ͭͯͷݕఆ
    :ˡ4/1ڞมྔɹ㱺ɹ4/1ʹ͍ͭͯͷݕఆɹŋŋŋҎԼಉ༷
    (FOPUZQFDPEJOH
    $PWBSJBUFT
    XIFSF Gi
    2 {0, 1, 2}
    Ei
    logit[Pr(Yi = 1)] = logit[⇡i( 0, e, g)] = 0 + eEi + gGi
    ⇡i = Pr(Yi = 1)

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  20. GENOTYPE AND EXPOSURE MISCLASSIFICATION (1) (p. 570)
    20
    /POEJ⒎FSFOUJBMNJTDMBTTJpDBUJPOʢඇࠩҟޡ෼ྨʣ͸
    όΠΦϚʔΧʔʢ஋ʣͱΞ΢τΧϜͱͷؔ࿈Λرऍ͢Δ
    ଞͷม਺ͱແؔ܎ͳޡ෼ྨʢؔ܎͢Δͷ͸ࠩҟޡ෼ྨʣ$IBQ
    /VMMํ޲΁ಇ͘
    ਖ਼֬ͳ෼ྨ ඇࠩҟ෼ྨΛͨ͠৔߹
    (-)ͷ20%→(+)
    (-)ͷ20%→(+)
    (+)ͷ20%→(-)
    Biomarker Biomarker Biomarker
    Clinical
    outcome
    + - + - + -
    Present 250 450 360 360 410 290
    Absent 100 900 720 280 740 260
    Odds Ratio 5.0 2.4 2.0
    Kenneth J. Rothman, ༁ʢຊా߶, ྛ༤Ұ, & ࠤ౻ت࿨ʣ. ϩεϚϯͷӸֶ ୈ2൛, 2013.ͷද7-6Λࢀߟʹ࡞੒

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  21. GENOTYPE AND EXPOSURE MISCLASSIFICATION (2) (p. 570)
    21
    w ࿈࠯ෆฏߧঢ়ଶ͕ڧ͍όϦΞϯτ͸ɼ࣬ױͱͷؔ࿈͕ڧ͘ͳΔ
    w ੈ୅͕ܦͭʹͭΕɼ࿈࠯ෆฏߧঢ়ଶ͕ऑ͘ͳΓɼ࣬ױͱͷؔ࿈͸رऍ͞ΕΔ
    ୈੈ୅
    Oੈ୅
    ࣬ױͱؔ࿈ͷ͋ΔόϦΞϯτʢ"ʣ
    όϦΞϯτʢ"ʣͱڑ཭͕ۙ͘ɼOੈ୅ܦͬͯ΋࿈࠯ฏߧঢ়ଶʹͳ͍
    w Ҩ఻ࢠ͸ɼݮ਺෼྾ͷࡍʹ૊Έ׵͑Λى͜͢
    w ಉ͡છ৭ମͰɼڑ཭͕͍ۙҨ఻ࢠ࠲͸όϦΞϯτʢ"ʣͱ
    ηοτʹͳͬͯ఻ΘΔ
    w ͭͷҟͳΔόϦΞϯτͱͷؔ࿈ͷఔ౓Λ
    ࿈࠯ෆฏߧʢ-JOLBHFEFTFRVJMJCSJVNʣͱ͍͏
    ʢ૬ؔΈ͍ͨͳ΋ͷʣ
    w ؔ࿈͕ڧ͍ͱ͖ɼ࿈࠯ෆฏߧ͸ڧ͍
    ඇࠩҟޡ෼ྨʹΑΔ

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  22. GENE-ENVIRONMENT INTERACTION (1) (p. 570)
    22
    (FOFUJDGBDUPS (

    EJTFBTF
    &OWJSPONFOUBMGBDUPS &

    PS&YQPTVSF
    "MMIVNBOEJTFBTF͸Ҩ఻ͱ؀ڥཁҼͱͷ૬ޓ࡞༻͕ݪҼͰ͋Δ
    º
    .BSHJOBMʹධՁ͢Δͱɼ૬ޓ࡞༻͕ϚεΫ͞ΕΔ
    (FOFUJDGBDUPS (
    EJTFBTF
    EJTFBTF
    &OWJSPONFOUBMGBDUPS &

    PS&YQPTVSF
    Ҩ఻ཁҼʹΑΔϦεΫ
    ؀ڥཁҼʹΑΔϦεΫ

    View full-size slide

  23. GENE-ENVIRONMENT INTERACTION(2) (p. 570)
    23
    Exposure
    Geno-
    type
    Cases Controls Contrast Odds ratio Main information
    - - A00 B00 A OR00 = 1.0 (Reference) Common reference
    - + A01 B01 B B vs. A OR01 = A01B00
    /(A00B01) Genotype alone vs. none
    + - A10 B10 C C vs. A OR10 = A10B00
    /(A00B10)
    Environmental factor alone vs.
    none
    + + A11 B11 D D vs. A OR11 = A11B00
    /(A00B11)
    Join genotype and environmental
    factor vs. none
    Multiplicative interaction D/(B * C) Deviation from multiplicative modelʢ৐๏Ϟσϧʣof interaction
    Additive interaction D - (B + C - 1) Deviation from additive modelʢՃ๏Ϟσϧʣof interaction
    (FOF&OWJSPONFOU*OUFSBDUJPO"OBMZTJTJOB$BTF$POUSPM4UVEZ
    Ҩ఻؀ڥަޓ࡞༻ͷղੳ͸͜ͷද͕͓͢͢Ί
    w ৘ใͷϩε͕ͳ͍
    w ަޓ࡞༻ͷد༩͕෼͔Δ
    w ૉͷ৘ใ͕͋Δ͔Βɼ৴པ۠ؒ౳ͷܭࢉ΋Մೳ

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  24. EMERGING ANALYTIC COMPLEXITY(1) (p. 571)
    24
    ِཅੑͷ੍ޚʢଟॏੑͷ໰୊ʣ
    w (8"4Ͱ͸ଟ͘ͷ4/7ʹ͍ͭͯݕఆΛ͓͜ͳ͏ˠଟॏੑͷ໰୊
    w #POGFSSPOJิਖ਼Ͱ͸ɼ༗ҙਫ४͸º
    w ϕΠζతख๏΋։ൃ͞Ε͍ͯΔ
    খඪຊߴ࣍ݩσʔλ
    w QO໰୊
    w ม਺ʹൺֱͯ͠αϯϓϧαΠζ͕খ͍͞
    w ݟ্͔͚׬શʹ༧ଌͰ͖ΔϞσϧʢཁҼͷ૊Έ߹Θͤʣ͕๲େʹಘΒΕͯ͠
    ·͏
    w ࣍ݩͷढ͍
    w ૊Έ߹ΘͤʢHFOFHFOF HFOFFOWJSPONFOUBMJOUFSBDUJPOʣ͕രൃతʹ૿
    ͑Δ

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  25. EMERGING ANALYTIC COMPLEXITY(2) (p. 571)
    25
    /PWFMBOBMZUJDTUSBUFHJFT
    w ֊૚ܕճؼ෼ੳ
    w ϕΠζਪఆ
    w $PNCJOBUPSJBMQBSUJUJPOJOHNFUIPE $1.

    w .VMUJGBDUPSEJNFOTJPOBMJUZSFEVDUJPO .%3
    NFUIPE
    Flanders, W. D., & Khoury, M. J. (1996). Analysis of case-parental control studies: method for the study of associations between disease and genetic
    markers. American Journal of Epidemiology, 144(7), 696–703.

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  26. NONCONVENTIONAL EPIDEMIOLOGIC STUDIES (p. 573)
    26
    w $BTFPOMZTUVEJFT
    w $BTFQBSFOUTUVEJFT

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  27. CASE-ONLY STUDIES (p. 573)
    27
    $BTFPOMZEFTJHOʹ͍ͭͯ͸ɼ%S,*%ઌੜͷαΠτΛࢀߟʹͤͯ͞
    ͍͖ͨͩ·ͨ͠
    $BTF0OMZ%FTJHOʹ͍ͭͯʦҨ఻Ӹֶʧʛ(FOF&OWJSPONFOUBM*OUFSBDUJPO
    ʢIUUQTXXXESLJEOFUDBTFPOMZHFOFQJʣ
    w $BTFͷΈΛର৅ʹݚڀΛ͓͜ͳ͏ํ๏
    w (FOFHFOF (FOFFOWJSPONFOUBMJOUFSBDUJPOΛධՁͰ͖Δ
    Exposure Genotype Cases
    - - A00
    - + A01
    + - A10
    + + A11
    Case-only odds ratio = (A11A00)/(A10A01)
    ΑΓେ͖͍ͱ͖ɼ
    ަޓ࡞༻ͷՄೳੑ͕ࣔࠦ͞ΕΔ
    w .BJOF⒎FDUʢҨ఻ࢠ΍؀ڥ͕Ξ΢τΧϜʹ௚઀༩͑ΔӨڹʣ͸Θ͔Βͳ͍
    w Ҩ఻ࢠͱ؀ڥཁҼ͕ಠཱ͍ͯ͠Δඞཁ͕͋Δ

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  28. CASE-PARENT STUDIES (p. 575)
    28
    $BTF
    $POUSPM
    w ࣬ױΛൃ঱ͨ͠$BTFͷ਌Λ$POUSPMͱ͢ΔσβΠϯ
    w ਓछɼຽ଒ɼҨ఻తഎܠͱ͍ͬͨަབྷҼࢠΛऔΓআ͘͜ͱ͕Ͱ͖Δ
    w $BTFDPIPSUσβΠϯͷྨܕ
    Genotype
    + -
    Case A B
    Control C D

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  29. EXAMPLE 1: COLORECTAL CANCER (p. 575)
    29
    ߴස౓ͷ೑ͷઁऔ େ௎͕Μ
    )FUFSPDZMJDBNJOFT
    )$"T

    ൃ͕Μੑ෺࣭
    ैདྷͷӸֶ
    Ո଒ྺ
    հೖʹΑΓϦεΫ௿Լ
    Ҩ఻ࢠมҟ
    ΑΓऑ͍Ҩ఻ࢠมҟ ؀ڥཁҼ
    º
    Ҩ఻Ӹֶɾ෼ࢠӸֶ Ҩ఻ࢠ
    εΫϦʔχϯά
    ศதͷಛҟతͳ
    Ҩ఻ࢠมҟ
    ૣظൃݟ
    Ҩ఻ࢠϓϩϑΝΠϦϯά
    w αϒλΠϓʹ෼ྨ
    w ద੾ͳ࣏ྍΛબ୒

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  30. EXAMPLE 2: INFLAMMATORY BOWEL DISEASE (1) (p. 577)
    30
    w Ԍ঱ੑ௎࣬ױͱͯ͠Ϋϩʔϯපͱ௵ᙾੑେ௎ԌΛѻ͏
    w (8"4͕੒ޭΛऩΊͨ࣬ױ
    w (8"4ͷ݁Ռ͸ɼൃ঱ػংͷ࠶ߟΛଅͨ͠
    w ૊৫ଛইΛҾ͖ى͜͢৽ͨͳ෺࣭ͷൃݟ
    w Ϋϩʔϯපͷ࣏ྍ๏ͱͯ͠
    *-ʹର͢ΔϞϊΫϩφʔϧ߅ମΛ࢖༻ͨ͠ྟচࢼݧͷ࣮ࢪΛଅͨ͠
    ؔ࿈όϦΞϯτͷ਺
    ࣬ױ
    2007೥ΑΓલʹಉఆ͞Εͨ
    όϦΞϯτ
    2007೥͔Β2013೥த·Ͱʹಉఆ
    ͞ΕͨόϦΞϯτ
    Ϋϩʔϯප 3 (NOD2, IBD5, IL23R) 140
    ௵ᙾੑେ௎Ԍ 1 (IL23R) 133
    ଟൃੑߗԽ঱ 0 52
    ݪൃੑ୾ोੑ؊ߗม 0 28
    ؔઅϦ΢Ϛν 2 (PAD14, CTLA4) 30
    શ਎ੑΤϦςϚτʔσε 2 (PTPN22, IR5) 31
    1ܕ౶೘ප 3 (INS, PTPN22, IRF5) 40
    ೥ʹ࠷ॳͷ(8"4͕ൃද͞Εͨ
    Tom Strachan et al., ༁ʢੁ໺७෉, & ෱ౢٛޫʣ. Genetics and Genomics in MedicineʢήϊϜҩֶʣ, 2016.ͷද8.10Λࢀߟʹ࡞੒

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  31. ࢀߟจݙ
    ,FOOFUI+3PUINBO ༁ʢຊా߶ ྛ༤Ұ ࠤ౻ت࿨ʣϩεϚϯͷӸֶୈ൛ ࣰݪग़
    ൛৽ࣾ
    5PN4USBDIBOFUBM ༁ʢੁ໺७෉ ෱ౢٛޫʣήϊϜҩֶ ϝσΟΧϧɾαΠΤϯεɾ
    Πϯλʔφγϣφϧ
    ਫౡੁ໺७ࢠʢஶʣɾαΩϚΠίʢ࡞ըʣϚϯΨͰΘ͔ΔήϊϜҩֶ ༽౔ࣾ
    "OESFB4'PVMLFT ؂༁ʢ੢ࢁؽʣ࣮ફͰΘ͔Δʂ3ʹΑΔ౷ܭҨ఻ֶ ؙળग़൛
    ෌ా੣ ২໦༏෉ήϊϜσʔλղੳ ڞཱग़൛
    ాٶݩ ২໦༏෉ খ৿ཧήϊϜҩֶͷͨΊͷҨ఻౷ܭֶ ڞཱग़൛
    31

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  32. Discussion!!
    32

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