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], "pgs_portability": { "slope": -2.627416955875061, "intercept": 0.9756990580069411, "r2": 0.9712744428395967, "pearson_r": -0.9855325681273029, "n_points": 11, "ding_2023_reference_pearson": -0.95 }, "border_xam": { "border_2022_R2": 0.7432, "border_2022_R2_ci_low": 0.6702, "border_2022_R2_ci_high": 0.8162, "n_trait_pairs_significant": 132, "uk_biobank_spousal_pairs": 40697, "psychiatric_avg_xam_share_after_5_generations": 0.29, "examples": [ { "pair": "anxiety \u00d7 MDD", "xam_share_of_rg": 0.21, "ci": [ 0.17, 0.25 ] }, { "pair": "AUD \u00d7 schizophrenia", "xam_share_of_rg": 0.83, "ci": [ 0.59, 1.24 ] } ], "interpretation": "On average, ~29% of reported psychiatric cross-disorder genetic correlation is consistent with cross-trait assortative mating alone. For some pairs (AUD \u00d7 SCZ) it accounts for nearly all of the reported rg; for others (anxiety \u00d7 MDD) it accounts for ~20%. The model's V(A_LD) term is the within-trait analogue of this between-trait phenomenon." }, "genetic_nurture": [ { "trait": "educational_attainment", "beta_ratio": 0.299, "v_Ad": 0.15, "v_Ai": 0.01341015, "cov_term": 0.024667500000000002, "v_Ai_plus_cov": 0.038077650000000005, "v_Ai_share_of_h2": 0.033525374999999996 }, { "trait": "height", "beta_ratio": 0.05, "v_Ad": 0.78, "v_Ai": 0.0019500000000000003, "cov_term": 0.00936, "v_Ai_plus_cov": 0.01131, "v_Ai_share_of_h2": 0.002294117647058824 }, { "trait": "bmi", "beta_ratio": 0.07, "v_Ad": 0.5, "v_Ai": 0.0024500000000000004, "cov_term": 0.005600000000000001, "v_Ai_plus_cov": 0.008050000000000002, "v_Ai_share_of_h2": 0.0032666666666666673 }, { "trait": "iq_g", "beta_ratio": 0.45, "v_Ad": 0.45, "v_Ai": 0.09112500000000001, "cov_term": 0.08910000000000001, "v_Ai_plus_cov": 0.18022500000000002, "v_Ai_share_of_h2": 0.12150000000000001 }, { "trait": "iq_g_age5", "beta_ratio": 0.4, "v_Ad": 0.184, "v_Ai": 0.029440000000000004, "cov_term": 0.029440000000000004, "v_Ai_plus_cov": 0.05888000000000001, "v_Ai_share_of_h2": 0.14720000000000003 }, { "trait": "iq_g_age25", "beta_ratio": 0.4, "v_Ad": 0.5, "v_Ai": 0.08000000000000002, "cov_term": 0.08800000000000001, "v_Ai_plus_cov": 0.16800000000000004, "v_Ai_share_of_h2": 0.10126582278481014 }, { "trait": "big_five_avg", "beta_ratio": 0.1, "v_Ad": 0.423675, "v_Ai": 0.004236750000000001, "cov_term": 0.005507775000000001, "v_Ai_plus_cov": 0.009744525000000002, "v_Ai_share_of_h2": 0.009415000000000001 }, { "trait": "neuroticism", "beta_ratio": 0.1, "v_Ad": 0.427725, "v_Ai": 0.004277250000000001, "cov_term": 0.004704975000000001, "v_Ai_plus_cov": 0.008982225000000002, "v_Ai_share_of_h2": 0.009505000000000001 }, { "trait": "schizophrenia", "beta_ratio": 0.15, "v_Ad": 0.509155, "v_Ai": 0.0114559875, "cov_term": 0.0343679625, "v_Ai_plus_cov": 0.04582395, "v_Ai_share_of_h2": 0.01450125 }, { "trait": "bipolar", "beta_ratio": 0.15, "v_Ad": 0.6704880000000001, "v_Ai": 0.01508598, "cov_term": 0.018103176000000002, "v_Ai_plus_cov": 0.033189156000000004, "v_Ai_share_of_h2": 0.019341 }, { "trait": "mdd", "beta_ratio": 0.2, "v_Ad": 0.349465, "v_Ai": 0.013978600000000004, "cov_term": 0.01048395, "v_Ai_plus_cov": 0.024462550000000007, "v_Ai_share_of_h2": 0.037780000000000015 }, { "trait": "adhd", "beta_ratio": 0.2, "v_Ad": 0.49358, "v_Ai": 0.019743200000000006, "cov_term": 0.04442220000000001, "v_Ai_plus_cov": 0.06416540000000001, "v_Ai_share_of_h2": 0.02668000000000001 }, { "trait": "autism", "beta_ratio": 0.1, "v_Ad": 0.5119999999999999, "v_Ai": 0.00512, "cov_term": 0.023039999999999998, "v_Ai_plus_cov": 0.028159999999999998, "v_Ai_share_of_h2": 0.0064 }, { "trait": "smoking_initiation", "beta_ratio": 0.2, "v_Ad": 0.3, "v_Ai": 0.012000000000000002, "cov_term": 0.022800000000000004, "v_Ai_plus_cov": 0.034800000000000005, "v_Ai_share_of_h2": 0.024000000000000004 } ], "environmental_effects": { "n_exposures": 10, "rows": [ { "exposure": "lead_blood_1_to_10_ugdl", "outcome": "iq", "effect_size": -6.2, "unit": "IQ_pts", "ci_low": -8.6, "ci_high": -3.8, "design": "pooled_longitudinal", "causal_evidence": "strong", "source": "Lanphear_2005", "n": "1333", "notes": "International pooled analysis 7 cohorts; steeper slope at low concentrations" }, { "exposure": "schooling_per_year", "outcome": "iq", "effect_size": 3.4, "unit": "IQ_pts", "ci_low": 1.0, "ci_high": 5.0, "design": "quasi_experimental_meta", "causal_evidence": "strong", "source": "Ritchie_Tucker_Drob_2018", "n": "600000", "notes": "Meta-analysis 142 effect sizes / 42 datasets; persists into old age; instrumental-variable + regression-discontinuity + control-prior-IQ designs all converge" }, { "exposure": "iodine_severe_deficiency", "outcome": "iq", "effect_size": -10.0, "unit": "IQ_pts", "ci_low": -12.0, "ci_high": -8.0, "design": "observational_RCT", "causal_evidence": "strong", "source": "Bougma_2013", "n": "N_A", "notes": "Severe deficiency = ~10 pt cost; supplementation recovers ~8.7 pts" }, { "exposure": "prenatal_alcohol_FAS", "outcome": "iq", "effect_size": -30.0, "unit": "IQ_pts", "ci_low": -40.0, "ci_high": -20.0, "design": "observational", "causal_evidence": "strong", "source": "Streissguth_2004", "n": "N_A", "notes": "Mean IQ ~70 in full FAS; Mendelian-randomization confirms causation; threshold effect" }, { "exposure": "PM25_per_ugm3", "outcome": "iq", "effect_size": -0.27, "unit": "IQ_pts", "ci_low": -0.5, "ci_high": -0.05, "design": "observational_meta", "causal_evidence": "moderate", "source": "Aghaei_2024", "n": "N_A", "notes": "~25 papers; smaller per-unit than lead but exposure widespread" }, { "exposure": "severe_psychosocial_deprivation", "outcome": "iq", "effect_size": -15.0, "unit": "IQ_pts", "ci_low": -20.0, "ci_high": -10.0, "design": "natural_experiment", "causal_evidence": "strong", "source": "Nelson_BEIP_2007", "n": "136", "notes": "Bucharest Early Intervention Project; institutional vs foster vs control; recovery if intervention before ~24mo" }, { "exposure": "breastfeeding_vs_formula", "outcome": "iq", "effect_size": 3.2, "unit": "IQ_pts", "ci_low": 1.5, "ci_high": 5.0, "design": "RCT_PROBIT", "causal_evidence": "strong", "source": "Kramer_PROBIT_2008", "n": "17046", "notes": "PROBIT cluster-RCT in Belarus; effect persists to age 6.5; smaller effect in MR-confirmed studies" }, { "exposure": "adoption_high_to_low_SES", "outcome": "iq", "effect_size": -12.0, "unit": "IQ_pts", "ci_low": -15.0, "ci_high": -8.0, "design": "natural_experiment", "causal_evidence": "strong", "source": "Capron_Duyme_1996", "n": "38", "notes": "Cross-fostered French adoptees; SES gap 12 pts in adopted children" }, { "exposure": "malnutrition_severe_chronic", "outcome": "iq", "effect_size": -15.0, "unit": "IQ_pts", "ci_low": -20.0, "ci_high": -10.0, "design": "observational", "causal_evidence": "strong", "source": "Grantham_McGregor_2007", "n": "N_A", "notes": "Stunting + chronic protein-energy deficiency; reversible if intervention <2yr" }, { "exposure": "parenting_quality_within_normal", "outcome": "iq", "effect_size": 1.0, "unit": "IQ_pts", "ci_low": -1.0, "ci_high": 3.0, "design": "within_family_twin", "causal_evidence": "weak", "source": "Plomin_Daniels_1987_meta", "n": "N_A", "notes": "Within Western normal range; small or zero adult effect after C controlled; this is the famous null" } ], "schooling": 3.4, "lead": -6.2, "largest_negative": -30.0 }, "gxe_interactions": { "rows": [ { "study": "Tucker_Drob_Bates_2016_US", "sample": "US", "a_prime": 0.074, "se": 0.02, "n_pairs": "11340", "outcome_metric": "a_prime_Purcell_biometric", "significance": "p_lt_0.0005", "source": "Tucker_Drob_Bates_2016", "notes": "Pooled across US studies; a' = expected change in additive genetic regression coefficient per SD of SES; significant moderate Gene-by-SES" }, { "study": "Tucker_Drob_Bates_2016_nonUS", "sample": "non_US", "a_prime": -0.027, "se": 0.022, "n_pairs": "13586", "outcome_metric": "a_prime_Purcell_biometric", "significance": "p_eq_0.223", "source": "Tucker_Drob_Bates_2016", "notes": "Pooled across non-US (W. Europe / Australia / Israel); essentially zero, possibly slight reverse" }, { "study": "Tucker_Drob_Bates_2016_pooled", "sample": "pooled_all", "a_prime": 0.029, "se": 0.019, "n_pairs": "24926", "outcome_metric": "a_prime_Purcell_biometric", "significance": "p_eq_0.136", "source": "Tucker_Drob_Bates_2016", "notes": "Overall non-significant with substantial cross-national heterogeneity \u2014 the heterogeneity is the headline" }, { "study": "Turkheimer_2003", "sample": "US_low_SES", "a_prime": 0.1, "se": null, "n_pairs": "N_A", "outcome_metric": "h2_at_low_SES", "significance": "observational", "source": "Turkheimer_2003", "notes": "Famous original \u2014 IQ h2 ~0.10 in poorest US families" }, { "study": "Turkheimer_2003_high", "sample": "US_high_SES", "a_prime": 0.72, "se": null, "n_pairs": "N_A", "outcome_metric": "h2_at_high_SES", "significance": "observational", "source": "Turkheimer_2003", "notes": "...rising to ~0.72 in wealthiest US families" }, { "study": "Harden_2007", "sample": "US", "a_prime": 0.06, "se": 0.03, "n_pairs": "839", "outcome_metric": "a_prime_replication", "significance": "p_lt_0.05", "source": "Harden_2007", "notes": "Within-family adolescent twin US replication" }, { "study": "Spengler_2018_Germany", "sample": "Germany", "a_prime": -0.01, "se": 0.02, "n_pairs": "1640", "outcome_metric": "a_prime_replication", "significance": "p_eq_0.6", "source": "Spengler_2018", "notes": "German twin replication; null result consistent with non-US Tucker-Drob & Bates" } ], "US_a_prime": 0.074, "US_se": 0.02, "nonUS_a_prime": -0.027, "nonUS_se": 0.022, "pooled_a_prime": 0.029, "pooled_se": 0.019, "n_total_pairs": 24926, "interpretation": "G\u00d7SES interaction is significant in the US (a'=0.074) but null in non-US samples (a'=-0.027). The cross-national heterogeneity is consistent with the model's claim that V(I) is small at typical PGS-by-environment scale and surfaces only when environmental variance is wide enough to include extreme tails." }, "headlines": { "H1_method_gradient": { "claim": "twin h\u00b2 \u2265 SNP h\u00b2 \u2265 within-family h\u00b2 holds per-trait", "traits_with_observed_data": 15, "traits_where_holds": 9, "verdict": "mixed" }, "H2_AM_partition": { "claim": "V(A_LD) = m\u00b7h\u00b2 accounts for 10-25% of observed h\u00b2 in AM-strong traits", "EA_ALD_estimate": 0.08800000000000002, "height_ALD_estimate": 0.17339999999999997, "verdict": "supported" }, "H3_wilson_logistic": { "claim": "Logistic h\u00b2(t) fits Bouchard 2013 anchors within ~3pp", "max_residual_pp": 1.812315886384963, "fitted_h_inf": 0.8056966312798416, "fitted_t_50": 9.021571768202916, "fitted_k": 0.2698758881828189, "verdict": "supported" }, "H4_multivariate_D_gap": { "claim": "Equicorrelated D undershoots disattenuated D by ~2x for 16PF panel", "D_equicorrelated_observed": 1.0321535298059632, "D_disattenuated_latent": 2.71, "ratio_disattenuated_over_observed": 2.6255783870733445, "verdict": "supported_with_caveat" }, "H5_PGS_portability": { "claim": "Pearson r between genetic distance and PGS R\u00b2 is strongly negative", "Ding_2023_reported_r": -0.95, "replicated_pearson_on_curated_panel": -0.9855325681273029, "verdict": "supported" }, "H6_xAM_inflation": { "claim": "Phenotypic cross-mate correlations explain ~74% of variance in reported psychiatric cross-disorder genetic correlation; the xAM-alone projection \u03b3\u0302 averages 0.29 across 6 disorders \u00d7 5 generations (range 0.21 anxiety\u00d7MDD to 0.83 AUD\u00d7SCZ). \u03b3\u0302 is the ratio of xAM-alone-implied rg to empirical rg \u2014 values near 1 are consistent with xAM accounting for the entire correlation; values near 0 require additional shared biology.", "border_2022_R2": 0.7432, "psychiatric_avg_share": 0.29, "verdict": "supported" }, "H7_environmental_effects": { "claim": "The model's V(E_m) bucket is non-empty: published causal effect sizes for measured environments", "n_exposures": 10, "largest_negative_effect_iq_pts": -30.0, "schooling_effect_per_year": 3.4, "lead_effect_1_to_10": -6.2, "verdict": "supported" }, "H8_gxe_interaction": { "claim": "V(I) is small at typical PGS-by-environment scale, larger when environmental variance is wide enough to include extreme tails. Tucker-Drob & Bates 2016 meta-analysis: a' = 0.074 (US, p<.0005); a' = -0.027 (non-US, p=.22); cross-national heterogeneity consistent with the threshold-conditional reading.", "US_a_prime": 0.074, "nonUS_a_prime": -0.027, "verdict": "supported_conditional" } } }