Pleiotropy of UK Biobank metabolites
Data files
Oct 13, 2022 version files 27.90 GB
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Acetate_step2.txt
123.98 KB
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Acetoacetate_Acetone_step3.txt
133.98 KB
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Acetoacetate_Ala_step3.txt
133.90 KB
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Acetoacetate_bOHbutyrate_step3.txt
133.78 KB
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Acetoacetate_Citrate_step3.txt
134.12 KB
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Acetoacetate_Gln_step3.txt
134.13 KB
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Acetoacetate_Glucose_step3.txt
134.10 KB
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Acetoacetate_Gly_step3.txt
133.72 KB
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Acetoacetate_His_step3.txt
133.97 KB
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Acetoacetate_Ile_step3.txt
134.04 KB
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Acetoacetate_Lactate_step3.txt
133.80 KB
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Acetoacetate_Leu_step3.txt
133.94 KB
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Acetoacetate_Phe_step3.txt
134.08 KB
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Acetoacetate_Pyruvate_step3.txt
133.80 KB
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Acetoacetate_step2.txt
123.20 KB
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Acetoacetate_Tyr_step3.txt
134.06 KB
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Acetoacetate_Val_step3.txt
134.02 KB
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Acetoacetate.ancestry_inclusive.imp_stats.gz
867.97 MB
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Acetoacetate.european_ancestry.imp_stats.gz
864.56 MB
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Acetone_Ala_step3.txt
134.05 KB
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Acetone_bOHbutyrate_step3.txt
133.94 KB
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Acetone_Citrate_step3.txt
134.06 KB
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Acetone_Gln_step3.txt
133.90 KB
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Acetone_Glucose_step3.txt
134.10 KB
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Acetone_Gly_step3.txt
133.70 KB
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Acetone_His_step3.txt
134 KB
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Acetone_Ile_step3.txt
134.13 KB
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Acetone_Lactate_step3.txt
134.10 KB
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Acetone_Leu_step3.txt
134.22 KB
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Acetone_Phe_step3.txt
134.08 KB
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Acetone_Pyruvate_step3.txt
134.11 KB
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Acetone_step2.txt
124.60 KB
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Acetone_Tyr_step3.txt
134.03 KB
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Acetone_Val_step3.txt
134.15 KB
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Acetone.ancestry_inclusive.imp_stats.gz
869.19 MB
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Acetone.european_ancestry.imp_stats.gz
865.87 MB
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Ala_bOHbutyrate_step3.txt
133.76 KB
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Ala_Citrate_step3.txt
133.97 KB
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Ala_Gln_step3.txt
133.81 KB
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Ala_Glucose_step3.txt
133.66 KB
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Ala_Gly_step3.txt
133.87 KB
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Ala_His_step3.txt
133.82 KB
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Ala_Ile_step3.txt
133.34 KB
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Ala_Lactate_step3.txt
133.73 KB
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Ala_Leu_step3.txt
133.25 KB
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Ala_Phe_step3.txt
133.75 KB
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Ala_Pyruvate_step3.txt
133.53 KB
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Ala_step2.txt
128.18 KB
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Ala_Tyr_step3.txt
133.62 KB
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Ala_Val_step3.txt
133.25 KB
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Ala.ancestry_inclusive.imp_stats.gz
873.70 MB
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Ala.european_ancestry.imp_stats.gz
869.39 MB
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bOHbutyrate_step2.txt
124.83 KB
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bOHbutyrate.ancestry_inclusive.imp_stats.gz
870.66 MB
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bOHbutyrate.european_ancestry.imp_stats.gz
866.04 MB
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both.CAD.glm.logistic.hybrid
546.29 KB
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both.Cholesterol.glm.linear
557.44 KB
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both.hard.glm.logistic.hybrid
546.98 KB
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both.hardNoSR.glm.logistic.hybrid
546.83 KB
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both.HDL_cholesterol.glm.linear
564.44 KB
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both.LDL_direct.glm.linear
558.86 KB
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both.SHBG.glm.linear
543.38 KB
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both.soft.glm.logistic.hybrid
548.68 KB
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both.softNoSR.glm.logistic.hybrid
548.54 KB
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both.Testosterone.glm.linear
553.46 KB
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both.Triglycerides.glm.linear
557.72 KB
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both.Urea.glm.linear
559.20 KB
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Citrate_bOHbutyrate_step3.txt
133.84 KB
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Citrate_Gln_step3.txt
133.84 KB
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Citrate_Glucose_step3.txt
134.20 KB
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Citrate_Gly_step3.txt
133.94 KB
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Citrate_His_step3.txt
134.11 KB
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Citrate_Ile_step3.txt
134.27 KB
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Citrate_Lactate_step3.txt
133.89 KB
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Citrate_Leu_step3.txt
134.28 KB
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Citrate_Phe_step3.txt
134 KB
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Citrate_Pyruvate_step3.txt
133.80 KB
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Citrate_step2.txt
127.28 KB
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Citrate_Tyr_step3.txt
134.03 KB
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Citrate_Val_step3.txt
134.24 KB
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Citrate.ancestry_inclusive.imp_stats.gz
875.69 MB
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Citrate.european_ancestry.imp_stats.gz
871.51 MB
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Clinical_LDL_C_step2.txt
127.28 KB
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Gln_bOHbutyrate_step3.txt
134.04 KB
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Gln_Glucose_step3.txt
133.97 KB
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Gln_Gly_step3.txt
133.52 KB
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Gln_His_step3.txt
133.76 KB
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Gln_Ile_step3.txt
134.14 KB
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Gln_Lactate_step3.txt
134.12 KB
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Gln_Leu_step3.txt
134.09 KB
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Gln_Phe_step3.txt
134.16 KB
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Gln_Pyruvate_step3.txt
134.05 KB
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Gln_step2.txt
128.42 KB
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Gln_Tyr_step3.txt
134.03 KB
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Gln_Val_step3.txt
134.10 KB
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Gln.ancestry_inclusive.imp_stats.gz
878.19 MB
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Gln.european_ancestry.imp_stats.gz
872.93 MB
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Glucose_bOHbutyrate_step3.txt
133.76 KB
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Glucose_Gly_step3.txt
133.81 KB
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Glucose_His_step3.txt
133.93 KB
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Glucose_Ile_step3.txt
133.89 KB
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Glucose_Lactate_step3.txt
133.80 KB
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Glucose_Leu_step3.txt
133.84 KB
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Glucose_Phe_step3.txt
133.92 KB
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Glucose_Pyruvate_step3.txt
133.82 KB
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Glucose_step2.txt
125.60 KB
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Glucose_Tyr_step3.txt
133.84 KB
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Glucose_Val_step3.txt
133.73 KB
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Glucose.ancestry_inclusive.imp_stats.gz
870.74 MB
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Glucose.european_ancestry.imp_stats.gz
867 MB
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Gly_bOHbutyrate_step3.txt
133.66 KB
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Gly_His_step3.txt
134.27 KB
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Gly_Ile_step3.txt
133.92 KB
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Gly_Lactate_step3.txt
133.90 KB
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Gly_Leu_step3.txt
133.85 KB
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Gly_Phe_step3.txt
134.05 KB
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Gly_Pyruvate_step3.txt
134.04 KB
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Gly_step2.txt
129.88 KB
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Gly_Tyr_step3.txt
134.04 KB
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Gly_Val_step3.txt
133.89 KB
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Gly.ancestry_inclusive.imp_stats.gz
873.40 MB
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Gly.european_ancestry.imp_stats.gz
863.82 MB
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HDL_C_step2.txt
130.97 KB
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His_bOHbutyrate_step3.txt
133.92 KB
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His_Ile_step3.txt
134.16 KB
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His_Lactate_step3.txt
134.18 KB
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His_Leu_step3.txt
134.03 KB
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His_Phe_step3.txt
134.16 KB
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His_Pyruvate_step3.txt
134.24 KB
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His_step2.txt
124.38 KB
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His_Tyr_step3.txt
133.99 KB
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His_Val_step3.txt
134.08 KB
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His.ancestry_inclusive.imp_stats.gz
876.33 MB
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His.european_ancestry.imp_stats.gz
871.23 MB
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Ile_bOHbutyrate_step3.txt
133.93 KB
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Ile_Lactate_step3.txt
133.80 KB
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Ile_Leu_step3.txt
133.65 KB
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Ile_Phe_step3.txt
134.02 KB
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Ile_Pyruvate_step3.txt
133.92 KB
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Ile_step2.txt
124.81 KB
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Ile_Tyr_step3.txt
134.02 KB
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Ile_Val_step3.txt
133.50 KB
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Ile.ancestry_inclusive.imp_stats.gz
870.24 MB
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Ile.european_ancestry.imp_stats.gz
866.48 MB
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Lactate_bOHbutyrate_step3.txt
133.89 KB
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Lactate_Leu_step3.txt
133.79 KB
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Lactate_Phe_step3.txt
133.93 KB
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Lactate_Pyruvate_step3.txt
133.92 KB
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Lactate_step2.txt
125.82 KB
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Lactate_Tyr_step3.txt
133.97 KB
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Lactate_Val_step3.txt
133.66 KB
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Lactate.ancestry_inclusive.imp_stats.gz
871.07 MB
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Lactate.european_ancestry.imp_stats.gz
866.48 MB
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LDL_C_step2.txt
127.57 KB
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Leu_bOHbutyrate_step3.txt
133.90 KB
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Leu_Phe_step3.txt
134.04 KB
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Leu_Pyruvate_step3.txt
133.95 KB
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Leu_step2.txt
125.68 KB
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Leu_Tyr_step3.txt
134.06 KB
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Leu_Val_step3.txt
133.38 KB
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Leu.ancestry_inclusive.imp_stats.gz
871.08 MB
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Leu.european_ancestry.imp_stats.gz
867.38 MB
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none.CAD.glm.logistic.hybrid
546.62 KB
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none.Cholesterol.glm.linear
558.47 KB
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none.hard.glm.logistic.hybrid
548.39 KB
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none.hardNoSR.glm.logistic.hybrid
547.53 KB
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none.HDL_cholesterol.glm.linear
568.06 KB
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none.LDL_direct.glm.linear
559.87 KB
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none.SHBG.glm.linear
546.01 KB
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none.soft.glm.logistic.hybrid
549.86 KB
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none.softNoSR.glm.logistic.hybrid
550.52 KB
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none.Testosterone.glm.linear
556.38 KB
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none.Triglycerides.glm.linear
559.21 KB
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none.Urea.glm.linear
560.35 KB
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Phe_bOHbutyrate_step3.txt
133.90 KB
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Phe_Pyruvate_step3.txt
134.13 KB
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Phe_step2.txt
124.40 KB
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Phe_Tyr_step3.txt
133.93 KB
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Phe_Val_step3.txt
133.95 KB
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Phe.ancestry_inclusive.imp_stats.gz
872.33 MB
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Phe.european_ancestry.imp_stats.gz
867.46 MB
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Pyruvate_bOHbutyrate_step3.txt
133.91 KB
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Pyruvate_step2.txt
124.89 KB
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Pyruvate_Tyr_step3.txt
134.03 KB
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Pyruvate_Val_step3.txt
133.96 KB
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Pyruvate.ancestry_inclusive.imp_stats.gz
871.36 MB
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Pyruvate.european_ancestry.imp_stats.gz
867.56 MB
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README.conditional.txt
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README.gwas.txt
1.49 KB
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rs1247764225.CAD.glm.logistic.hybrid
546.46 KB
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rs1247764225.Cholesterol.glm.linear
557.86 KB
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rs1247764225.hard.glm.logistic.hybrid
548.13 KB
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rs1247764225.hardNoSR.glm.logistic.hybrid
547.55 KB
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rs1247764225.HDL_cholesterol.glm.linear
567.13 KB
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rs1247764225.LDL_direct.glm.linear
559.53 KB
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rs1247764225.SHBG.glm.linear
544.96 KB
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rs1247764225.soft.glm.logistic.hybrid
550.29 KB
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rs1247764225.softNoSR.glm.logistic.hybrid
550.59 KB
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rs1247764225.Testosterone.glm.linear
556.59 KB
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rs1247764225.Triglycerides.glm.linear
558.52 KB
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rs1247764225.Urea.glm.linear
559.52 KB
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rs61791721.CAD.glm.logistic.hybrid
546.29 KB
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rs61791721.Cholesterol.glm.linear
558.87 KB
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rs61791721.hard.glm.logistic.hybrid
546.94 KB
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rs61791721.hardNoSR.glm.logistic.hybrid
547.04 KB
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rs61791721.HDL_cholesterol.glm.linear
565.83 KB
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rs61791721.LDL_direct.glm.linear
560.10 KB
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rs61791721.SHBG.glm.linear
543.36 KB
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rs61791721.soft.glm.logistic.hybrid
549.04 KB
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rs61791721.softNoSR.glm.logistic.hybrid
549.01 KB
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rs61791721.Testosterone.glm.linear
552.54 KB
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rs61791721.Triglycerides.glm.linear
558.54 KB
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rs61791721.Urea.glm.linear
559.79 KB
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rs645040.CAD.glm.logistic.hybrid
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rs645040.Cholesterol.glm.linear
558.94 KB
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rs645040.hard.glm.logistic.hybrid
547.54 KB
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rs645040.hardNoSR.glm.logistic.hybrid
547.16 KB
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rs645040.HDL_cholesterol.glm.linear
565.61 KB
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rs645040.LDL_direct.glm.linear
560.33 KB
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rs645040.SHBG.glm.linear
543.21 KB
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rs645040.soft.glm.logistic.hybrid
549 KB
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rs645040.softNoSR.glm.logistic.hybrid
549.35 KB
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rs645040.Testosterone.glm.linear
552.93 KB
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rs645040.Triglycerides.glm.linear
558.51 KB
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rs645040.Urea.glm.linear
559.76 KB
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rs687339.CAD.glm.logistic.hybrid
546.48 KB
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rs687339.Cholesterol.glm.linear
559.05 KB
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rs687339.hard.glm.logistic.hybrid
547.40 KB
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rs687339.hardNoSR.glm.logistic.hybrid
547 KB
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rs687339.HDL_cholesterol.glm.linear
565.56 KB
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rs687339.LDL_direct.glm.linear
560.34 KB
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rs687339.SHBG.glm.linear
543.16 KB
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rs687339.soft.glm.logistic.hybrid
549.12 KB
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rs687339.softNoSR.glm.logistic.hybrid
549.30 KB
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rs687339.Testosterone.glm.linear
552.77 KB
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rs687339.Triglycerides.glm.linear
558.48 KB
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Total_FA_step2.txt
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Total_FC_step2.txt
128.17 KB
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Total_TG_step2.txt
130.20 KB
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Tyr_bOHbutyrate_step3.txt
134.08 KB
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Tyr_step2.txt
127.13 KB
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Tyr_Val_step3.txt
134.05 KB
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Tyr.ancestry_inclusive.imp_stats.gz
872.96 MB
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Tyr.european_ancestry.imp_stats.gz
868.85 MB
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Val_bOHbutyrate_step3.txt
133.88 KB
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Val_step2.txt
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Val.ancestry_inclusive.imp_stats.gz
874.49 MB
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Val.european_ancestry.imp_stats.gz
870.11 MB
Abstract
Pleiotropy and genetic correlation are widespread features in GWAS, but they are often difficult to interpret at the molecular level. Here, we perform GWAS of 16 metabolites clustered at the intersection of amino acid catabolism, glycolysis, and ketone body metabolism in a subset of UK Biobank. We utilize the well-documented biochemistry jointly impacting these metabolites to analyze pleiotropic effects in the context of their pathways. Among the 213 lead GWAS hits, we find a strong enrichment for genes encoding pathway-relevant enzymes and transporters. We demonstrate that the effect directions of variants acting on biology between metabolite pairs often contrast with those of upstream or downstream variants as well as the polygenic background. Thus, we find that these outlier variants often reflect biology local to the traits. Finally, we explore the implications for interpreting disease GWAS, underscoring the potential of unifying biochemistry with dense metabolomics data to understand the molecular basis of pleiotropy in complex traits and diseases.
The details of the dataset processing are provided in our manuscript: https://elifesciences.org/articles/79348
Briefly, we performed GWAS of technically-corrected metabolite levels from the Nightingale NMR Metabolomics dataset on 94,464 European-ancestry individuals and 98,189 individuals in our ancestry-inclusive analysis using BOLT-REML and integrated these results with a curated biochemical map connecting the 16 core metabolites spanning glycolysis, ketones, and amino acids.
Files with names "*_step3.txt" and "*_step2.txt" are the local genetic correlation and local heritability estimates for each approximately independent LD block (Berisa et al. 2016) using rho-HESS (Shi et al. 2017) and HESS (Shi et al. 2016), respectively. These were derived from European-ancestry summary statistics.
Files with names that start with a SNP identifier, "both," or "neither" are the conditional fine-mapping summary statistics from our example loci, generated with the PLINK2 "--condition" option. Please see the manucript for additional details.
These data are in standard compressed text format and specialty software is not necessary to open the files. For help with using these data, please reach out to the corresponding authors of the corresponding manuscript: https://elifesciences.org/articles/79348