{
  "task_slug": "endo-site-arthritis-shared-loci",
  "question": "内异症与炎性关节炎之间的胚系遗传共享，是否随子宫内膜异位病灶的解剖部位而不同？",
  "falsifiable_prediction": "合并内异症表型与类风湿锚点方向一致性显著高于MAF匹配零分布(p<0.05)，但四个部位亚型相对合并表型的Δ的95% bootstrap CI全部覆盖0。",
  "prediction_outcome": "inconclusive",
  "negative_result": true,
  "dataset": "FinnGen R13 公开GWAS汇总统计，10个phenocode，流式curl|zcat|mawk读取，未落盘完整文件；共同参考骨架(10kb窗口,0.01<af<0.99)=283340个位点。",
  "env": {
    "python": "3.12.3",
    "torch": "2.13.0+cpu",
    "extra_packages": []
  },
  "seeds": [
    0,
    1,
    2
  ],
  "arms": [
    {
      "name": "baseline-pooled-endometriosis",
      "is_baseline": true,
      "what": "N14_ENDOMETRIOSIS(pooled) vs primary anchor M13_RHEUMA at 41 clumped lead SNPs (p<5e-08, 1000kb distance clump, MHC excluded).",
      "metrics": {
        "sign_concordance": {
          "per_seed": [
            0.463415,
            0.463415,
            0.463415
          ],
          "mean": 0.463415,
          "std": 0.0
        },
        "ivw_slope": {
          "per_seed": [
            -0.023577,
            -0.023577,
            -0.023577
          ],
          "mean": -0.023577,
          "std": 0.0
        },
        "empirical_p_sign_concordance": {
          "per_seed": [
            0.784216,
            0.802198,
            0.801199
          ],
          "mean": 0.795871,
          "std": 0.008251
        },
        "empirical_p_ivw_slope": {
          "per_seed": [
            0.88012,
            0.896104,
            0.888112
          ],
          "mean": 0.888112,
          "std": 0.006525
        },
        "scaffold_retention_frac": {
          "per_seed": [
            1.0006,
            1.0006,
            1.0006
          ],
          "mean": 1.0006,
          "std": 0.0
        }
      }
    },
    {
      "name": "baseline-maf-matched-null-snps",
      "is_baseline": true,
      "what": "MAF-matched (+/-0.02), >=1Mb-from-any-lead-SNP null pool drawn from the common scaffold, 1000 draws x 3 seeds, anchor=M13_RHEUMA/pooled endo.",
      "metrics": {
        "null_mean_sign_concordance": {
          "per_seed": [
            0.514122,
            0.519902,
            0.517341
          ],
          "mean": 0.517122,
          "std": 0.002365
        },
        "null_mean_ivw_slope": {
          "per_seed": [
            0.04166,
            0.047679,
            0.043602
          ],
          "mean": 0.044313,
          "std": 0.002508
        },
        "null_pool_size": {
          "per_seed": [
            275779.0,
            275779.0,
            275779.0
          ],
          "mean": 275779.0,
          "std": 0.0
        }
      }
    },
    {
      "name": "proposed-site-ovary",
      "is_baseline": false,
      "what": "N14_ENDOMETRIOSIS_OVARY vs primary anchor M13_RHEUMA at 41 lead SNPs; delta = this site's stat minus pooled-endometriosis's stat, paired-locus bootstrap 95% CI (1000x3 seeds).",
      "metrics": {
        "sign_concordance": {
          "per_seed": [
            0.439024,
            0.439024,
            0.439024
          ],
          "mean": 0.439024,
          "std": 0.0
        },
        "ivw_slope": {
          "per_seed": [
            -0.07431,
            -0.07431,
            -0.07431
          ],
          "mean": -0.07431,
          "std": 0.0
        },
        "empirical_p_sign_concordance": {
          "per_seed": [
            0.84016,
            0.852148,
            0.868132
          ],
          "mean": 0.85348,
          "std": 0.011458
        },
        "empirical_p_ivw_slope": {
          "per_seed": [
            0.744256,
            0.74026,
            0.761239
          ],
          "mean": 0.748585,
          "std": 0.009095
        },
        "delta_vs_pooled_sign_concordance": {
          "per_seed": [
            -0.01839,
            -0.026488,
            -0.02778
          ],
          "mean": -0.02422,
          "std": 0.004156,
          "ci_low": -0.170732,
          "ci_high": 0.121951,
          "covers_zero": true,
          "observed_delta": -0.02439
        },
        "delta_vs_pooled_ivw_slope": {
          "per_seed": [
            -0.051352,
            -0.054121,
            -0.054458
          ],
          "mean": -0.05331,
          "std": 0.001392,
          "ci_low": -0.122364,
          "ci_high": 0.003183,
          "observed_delta": -0.050733
        },
        "min_detectable_delta": {
          "per_seed": [
            0.203152,
            0.203152,
            0.203152
          ],
          "mean": 0.203152,
          "std": 0.0
        },
        "scaffold_retention_frac": {
          "per_seed": [
            1.0006,
            1.0006,
            1.0006
          ],
          "mean": 1.0006,
          "std": 0.0
        }
      }
    },
    {
      "name": "proposed-site-pelvicperitoneum",
      "is_baseline": false,
      "what": "N14_ENDOMETRIOSIS_PELVICPERITONEUM vs primary anchor M13_RHEUMA at 41 lead SNPs; delta = this site's stat minus pooled-endometriosis's stat, paired-locus bootstrap 95% CI (1000x3 seeds).",
      "metrics": {
        "sign_concordance": {
          "per_seed": [
            0.463415,
            0.463415,
            0.463415
          ],
          "mean": 0.463415,
          "std": 0.0
        },
        "ivw_slope": {
          "per_seed": [
            -0.031667,
            -0.031667,
            -0.031667
          ],
          "mean": -0.031667,
          "std": 0.0
        },
        "empirical_p_sign_concordance": {
          "per_seed": [
            0.743257,
            0.776224,
            0.778222
          ],
          "mean": 0.765901,
          "std": 0.016033
        },
        "empirical_p_ivw_slope": {
          "per_seed": [
            0.893107,
            0.872128,
            0.908092
          ],
          "mean": 0.891109,
          "std": 0.01475
        },
        "delta_vs_pooled_sign_concordance": {
          "per_seed": [
            0.003951,
            0.000415,
            -0.003171
          ],
          "mean": 0.000398,
          "std": 0.002908,
          "ci_low": -0.146341,
          "ci_high": 0.146341,
          "covers_zero": true,
          "observed_delta": 0.0
        },
        "delta_vs_pooled_ivw_slope": {
          "per_seed": [
            -0.011725,
            -0.013303,
            -0.014481
          ],
          "mean": -0.01317,
          "std": 0.001129,
          "ci_low": -0.082755,
          "ci_high": 0.050883,
          "observed_delta": -0.008089
        },
        "min_detectable_delta": {
          "per_seed": [
            0.213237,
            0.213237,
            0.213237
          ],
          "mean": 0.213237,
          "std": 0.0
        },
        "scaffold_retention_frac": {
          "per_seed": [
            1.0006,
            1.0006,
            1.0006
          ],
          "mean": 1.0006,
          "std": 0.0
        }
      }
    },
    {
      "name": "proposed-site-uterus-adenomyosis",
      "is_baseline": false,
      "what": "N14_ENDOMETRIOSIS_UTERUS vs primary anchor M13_RHEUMA at 41 lead SNPs; delta = this site's stat minus pooled-endometriosis's stat, paired-locus bootstrap 95% CI (1000x3 seeds).",
      "metrics": {
        "sign_concordance": {
          "per_seed": [
            0.658537,
            0.658537,
            0.658537
          ],
          "mean": 0.658537,
          "std": 0.0
        },
        "ivw_slope": {
          "per_seed": [
            0.053939,
            0.053939,
            0.053939
          ],
          "mean": 0.053939,
          "std": 0.0
        },
        "empirical_p_sign_concordance": {
          "per_seed": [
            0.045954,
            0.028971,
            0.044955
          ],
          "mean": 0.03996,
          "std": 0.007781
        },
        "empirical_p_ivw_slope": {
          "per_seed": [
            0.831169,
            0.825175,
            0.837163
          ],
          "mean": 0.831169,
          "std": 0.004894
        },
        "delta_vs_pooled_sign_concordance": {
          "per_seed": [
            0.194561,
            0.195293,
            0.195366
          ],
          "mean": 0.195073,
          "std": 0.000363,
          "ci_low": 0.02439,
          "ci_high": 0.365854,
          "covers_zero": false,
          "observed_delta": 0.195122
        },
        "delta_vs_pooled_ivw_slope": {
          "per_seed": [
            0.079286,
            0.082019,
            0.082537
          ],
          "mean": 0.081281,
          "std": 0.001426,
          "ci_low": 0.018511,
          "ci_high": 0.160838,
          "observed_delta": 0.077517
        },
        "min_detectable_delta": {
          "per_seed": [
            0.24414,
            0.24414,
            0.24414
          ],
          "mean": 0.24414,
          "std": 0.0
        },
        "scaffold_retention_frac": {
          "per_seed": [
            1.0006,
            1.0006,
            1.0006
          ],
          "mean": 1.0006,
          "std": 0.0
        }
      }
    },
    {
      "name": "proposed-site-rectovaginal",
      "is_baseline": false,
      "what": "N14_ENDOMETRIOSIS_RECTPVAGSEPT_VAGINA vs primary anchor M13_RHEUMA at 41 lead SNPs; delta = this site's stat minus pooled-endometriosis's stat, paired-locus bootstrap 95% CI (1000x3 seeds).",
      "metrics": {
        "sign_concordance": {
          "per_seed": [
            0.512195,
            0.512195,
            0.512195
          ],
          "mean": 0.512195,
          "std": 0.0
        },
        "ivw_slope": {
          "per_seed": [
            -0.030226,
            -0.030226,
            -0.030226
          ],
          "mean": -0.030226,
          "std": 0.0
        },
        "empirical_p_sign_concordance": {
          "per_seed": [
            0.566434,
            0.549451,
            0.557443
          ],
          "mean": 0.557776,
          "std": 0.006937
        },
        "empirical_p_ivw_slope": {
          "per_seed": [
            0.935065,
            0.924076,
            0.928072
          ],
          "mean": 0.929071,
          "std": 0.004542
        },
        "delta_vs_pooled_sign_concordance": {
          "per_seed": [
            0.050415,
            0.047732,
            0.04439
          ],
          "mean": 0.047512,
          "std": 0.002464,
          "ci_low": -0.121951,
          "ci_high": 0.219512,
          "covers_zero": true,
          "observed_delta": 0.04878
        },
        "delta_vs_pooled_ivw_slope": {
          "per_seed": [
            -0.005321,
            -0.003979,
            -0.006966
          ],
          "mean": -0.005422,
          "std": 0.001222,
          "ci_low": -0.089809,
          "ci_high": 0.081877,
          "observed_delta": -0.006649
        },
        "min_detectable_delta": {
          "per_seed": [
            0.234467,
            0.234467,
            0.234467
          ],
          "mean": 0.234467,
          "std": 0.0
        },
        "scaffold_retention_frac": {
          "per_seed": [
            1.0006,
            1.0006,
            1.0006
          ],
          "mean": 1.0006,
          "std": 0.0
        }
      }
    },
    {
      "name": "control-positive-leiomyoma",
      "is_baseline": false,
      "what": "CD2_BENIGN_LEIOMYOMA_UTERI as anchor vs pooled endometriosis at 111 lead SNPs (known shared genetic origin; must show significant concordance or the pipeline lacks power).",
      "metrics": {
        "sign_concordance": {
          "per_seed": [
            0.810811,
            0.810811,
            0.810811
          ],
          "mean": 0.810811,
          "std": 0.0
        },
        "ivw_slope": {
          "per_seed": [
            0.302131,
            0.302131,
            0.302131
          ],
          "mean": 0.302131,
          "std": 0.0
        },
        "empirical_p_sign_concordance": {
          "per_seed": [
            0.000999,
            0.000999,
            0.000999
          ],
          "mean": 0.000999,
          "std": 0.0
        },
        "empirical_p_ivw_slope": {
          "per_seed": [
            0.557443,
            0.553447,
            0.575425
          ],
          "mean": 0.562105,
          "std": 0.009559
        },
        "scaffold_retention_frac": {
          "per_seed": [
            1.0006,
            1.0006,
            1.0006
          ],
          "mean": 1.0006,
          "std": 0.0
        }
      }
    },
    {
      "name": "control-negative-myopia",
      "is_baseline": false,
      "what": "H7_MYOPIA as anchor vs pooled endometriosis at 7 lead SNPs (unrelated trait; must NOT show significant concordance or the pipeline reports artifacts).",
      "metrics": {
        "sign_concordance": {
          "per_seed": [
            0.571429,
            0.571429,
            0.571429
          ],
          "mean": 0.571429,
          "std": 0.0
        },
        "ivw_slope": {
          "per_seed": [
            -0.000104,
            -0.000104,
            -0.000104
          ],
          "mean": -0.000104,
          "std": 0.0
        },
        "empirical_p_sign_concordance": {
          "per_seed": [
            0.503497,
            0.512488,
            0.528472
          ],
          "mean": 0.514819,
          "std": 0.010328
        },
        "empirical_p_ivw_slope": {
          "per_seed": [
            1.0,
            1.0,
            1.0
          ],
          "mean": 1.0,
          "std": 0.0
        },
        "scaffold_retention_frac": {
          "per_seed": [
            1.0006,
            1.0006,
            1.0006
          ],
          "mean": 1.0006,
          "std": 0.0
        }
      }
    }
  ],
  "headline": {
    "metric": "sign_concordance",
    "baseline_mean": 0.463415,
    "proposed_mean": 0.518293,
    "delta": 0.054878,
    "claim": "以M13_RHEUMA为锚点,合并内异症表型方向一致性=0.463(经验p=0.796)；部分部位亚型的Δ的95%CI不覆盖0。 结果不确定:primary anchor (rheuma) vs pooled endo did not reach significant concordance。"
  },
  "deviations": [
    "预算(45分钟)内只完整跑通了主参数配置:anchor_p_threshold=5e-8、clump_window_kb=1000、MHC排除。原计划sweep里的 500kb窗口 / MHC纳入 / anchor_p=1e-5 三个维度未做完整网格重跑,只用5e-8+1000kb+MHC排除这一组作为唯一正式结果。",
    "SPONDYLOARTHRITIS、M13_PSORIARTH 两个次要关节炎锚点的 site-vs-pooled Δ 已计算,写入了 logs/run.log,用于交叉检验 uterus 位点在M13_RHEUMA锚点下的孤立信号是否可复现;但未整合进 results.json 的 arms/headline(schema里的headline只认单一baseline/proposed口径)。结论见NOTES.md:不可复现,判定为多重比较下的偶然结果。",
    "MHC区域(chr6:25-34Mb)在主分析中被排除,未做'纳入MHC'的敏感性分析。",
    "共同参考骨架(scaffold retention的分母)取H7_MYOPIA的genome-wide 10kb-thinning骨架作为参考文件,而不是原计划文字里写的N14_ENDOMETRIOSIS,因为myopia是流程里第一个抓取、用来锚定target_scaffold的文件;10个文件的retention全部为1.0000-1.0006,说明FinnGen R13不同表型间变异集合(chrom:pos:ref:alt)几乎完全一致。",
    "falsifiable_prediction的前提条件(合并内异症表型与M13_RHEUMA方向一致性显著高于零分布)在真实数据上未成立(观测sign_concordance=0.463,低于0.5,经验p=0.796),因此四个部位亚型的Δ检验属于'条件不成立下的探索性结果',prediction_outcome判定为inconclusive而非confirmed/refuted,细节见NOTES.md。"
  ],
  "runtime_sec": 16.0
}