Analysis Summary: Hypermobility Beighton Score
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1 Analysis Summary: Hypermobility Beighton Score Phenotype Description The beighton_hypermobility_qtl phenotype comes from: morphology survey: Can you bring your right thumb to reach your forearm (see above image)?(right_thumb_flexibility) (Yes, No, I m not sure) Can you bring your left thumb to reach your forearm? (left_thumb_flexibility) (Yes, No, I m not sure) Can you extend your right forearm backwards to form a greater than 180 degree angle at your elbow (see above image)? (right_elbow_hyper) (Yes, No, I m not sure) Can you extend your left forearm backwards to form a greater than 180 degree angle at your elbow? (left_elbow_hyper) (Yes, No, I m not sure) Can you extend your lower left leg forward to form a greater than 180 degree angle at your knee (see above image)? (left_knee_hyper) (Yes, No, I m not sure) Can you extend your lower right leg forward to form a greater than 180 degree angle at your knee? (right_knee_hyper) (Yes, No, I m not sure) Can you bend down and place your entire palms on the floor while keeping your legs straight (see above image)? (palms_on_floor) (Yes, No, I m not sure) When you place your right hand flat on a table, can you lift your right little finger straight up to a vertical position or even further? (right_finger_flex) (Yes, No, I m not sure) When you place your left hand flat on a table, can you lift your left little finger straight up to a vertical position or even further? (left_finger_flex) (Yes, No, I m not sure) Each question has three choices (yes, no, not sure). The beighton_hypermobility_qtl is the total counts of the positive answers to the 9 questions regarding joint mobility (beighton score). It was scored 0 9, higher scores signal greater hypermobility. We set NAs when people who didn t answer. Phenotype Statistics The following table shows demographics of unrelated, European individuals included in the GWAS. Phenotype Group Total M F (0,30] (30,45] (45,60] (60,Inf] beighton_hypermobility_qtl [0,1] (1,2] (2,3] (3,5] (5,9] The following table shows the phenotypic distribution across 23andMe genotyping platforms for individuals included in the GWAS. Phenotype Group Total v1/v2 v3 v4 beighton_hypermobility_qtl [0,1] (1,2] (2,3] (3,5] (5,9] Null Model with Covariates The following table shows results of fitting a model for the trait based on just the covariates. Principal coordinates have been standardized, so these effect sizes are in units of standard deviations. Estimate Std. Error t value Pr(> t ) age sexf pc pc pc pc pc Q Q plot of scaled residuals Nature Genetics: doi: /ng.3570
2 SNP level QC information The following table shows results for QC filters on the genotyped data: failed passed no filters not V1 only, chrm, chry parent offspring test MAF > 0% HWE > 1e gt.rate > 90% batch effects The following table shows results for QC filters on the imputed dosage data: failed passed no filters MAF > 0% imputation quality batch effects The following table shows results for QC filters on the merged association test results: passed total imputed only both passed genotyped only no test result MAF < 0.1% Genetic Association Tests We performed linear regression assuming an additive model for allelic effects, using the model: beighton_hypermobility_qtl ~ age + sex + pc.0 + pc.1 + pc.2 + pc.3 + pc.4 + genotype This genome wide association analysis includes data from individuals of European ancestry, filtered to remove close relatives. The results in this report have been adjusted for a genomic control inflation factor λ= The equivalent inflation factor rescaled for a sample size of 2000 would be λ 2000 = 1.003, and for 20000, λ = Manhattan Plot Nature Genetics: doi: /ng.3570
3 Q Q Plot of GWAS Results Index SNPs for Strongest Associations cytoband assay.name scaffold position alleles src pvalue effect 95% CI gene.context 20q11.22 rs chr A/G I [ 0.100, 0.057] [GDF5] 6q25.3 rs chr C/T I [ 0.226, 0.128] [FNDC1] 6p21.32 rs chr C/T I [ 0.102, 0.058] [NOTCH4] 2q37.3 rs chr A/G I [0.062,0.111] C2orf54 [] SNED1 16q24.3 rs chr C/T I [ 0.133, 0.074] [PIEZO1] 3q12.2 rs chr C/T I [0.056,0.101] [ABI3BP] 17q21.31 rs chr C/T I [ 0.116, 0.063] LRRC37A3 [] CRHR1 15q24.1 rs chr D/I I [ 0.098, 0.052] [LOXL1] 6q14.1 rs chr C/T I [ 0.090, 0.047] [BCKDHB] 21q22.11 rs chr C/G I [0.044,0.088] MRPS6 [] KCNE2 8p23.1 rs chr C/G I [ 0.090, 0.045] [XKR6] 17q24.1 rs chr A/G I [ 0.097, 0.048] SMURF2 [] PLEKHM1P 15q21.3 rs chr G/T I [0.046,0.094] PRTG [] NEDD4 5q14.3 rs chr C/T I [0.101,0.211] [VCAN] 8p23.1 rs chr G/T I [ 0.080, 0.037] PPP1R3B [] TNKS 2p16.3 rs chr C/G I [ 0.096, 0.045] PPP1R21 [] STON1 GTF2A1L 2p16.1 rs chr A/G I [ 0.092, 0.042] [EFEMP1] 1p32.3 rs chr A/G I [0.049,0.108] ZCCHC11 [] GPX7 6q27 rs1040 chr C/T I [ 0.078, 0.035] [THBS2] 6q14.1 rs chr C/G I [ 0.149, 0.067] [COL12A1] 8p23.1 rs chr C/G I [3.087,6.963] [MSRA] 17p12 rs chr A/G I [ 0.123, 0.054] [ARHGAP44] Nature Genetics: doi: /ng.3570
4 13q11 rs chr A/C I [0.046,0.107] [] TUBA3C 4p15.32 rs chr G/T I [ 0.097, 0.042] C1QTNF7 [] CC2D2A 6p12.1 rs chr A/G I [0.045,0.104] [COL21A1] Quality Statistics for Index SNPs assay.name is.v2 is.v3 is.v4 gt.rate hw.p.value p.date freq.b avg.rsqr min.rsqr p.batch dose.b qc.mask rs FALSE TRUE TRUE v2v3v4 rs FALSE FALSE FALSE v2v3v4 rs FALSE FALSE FALSE v2v3v4 rs FALSE FALSE FALSE v2v3v4 rs FALSE FALSE FALSE v2v3v4 rs FALSE FALSE FALSE v2v3v4 rs FALSE FALSE FALSE v2v3v4 rs FALSE FALSE FALSE v2v3v4 rs FALSE FALSE FALSE v2v3v4 rs FALSE FALSE FALSE v2v3v4 rs FALSE FALSE FALSE v2v3v4 rs FALSE TRUE FALSE v2v3v4 rs FALSE TRUE FALSE v2v3v4 rs FALSE FALSE FALSE v2v3v4 rs FALSE FALSE FALSE v2v3v4 rs FALSE FALSE FALSE v2v3v4 rs TRUE TRUE TRUE v2v3v4 rs FALSE TRUE FALSE v2v3v4 rs1040 FALSE FALSE FALSE v2v3v4 rs FALSE FALSE FALSE v2v3v4 rs FALSE FALSE FALSE v4 rs TRUE TRUE TRUE v2v3v4 rs TRUE TRUE TRUE v2v3v4 rs FALSE FALSE FALSE v2v3v4 rs FALSE FALSE FALSE v2v3v4 SNP Statistics in the GWAS Sample assay.name AA.0 AB.0 BB.0 im.num.0 dose.b.0 rs rs rs rs rs rs rs rs rs rs rs rs rs rs rs rs rs rs rs rs rs rs rs rs rs Annotations from NHGRI GWAS Catalog The following table shows, for each index SNP, all entries in the NHGRI GWAS Catalog that are within 500kb and in at least moderate linkage disequilibrium (r 2 > 0.5). region position our.name our.pval dist rsqr assay.name pvalue pubmed.id trait genes 20q rs rs Height GDF5,UQCC 20q rs rs Height BFZB 20q rs rs Height UQCC, GDF5, 20q rs rs Spine bone size UQCC 20q rs rs Height GDF5 20q rs rs Height UQCC 20q rs rs Height GDF5 20q rs rs Height GDF5 17q rs rs Parkinson s disease PLEKHM1, MAPT, IMP5 17q rs rs Ovarian cancer in BRCA1 mutation carriers 17q rs rs Parkinson s disease MAPT 17q rs rs Parkinson s disease MAPT, C17orf69, 17q rs rs Parkinson s disease MAPT 17q rs rs Male pattern baldness Intergenic 17q rs rs Bone mineral density MAPT Nature Genetics: doi: /ng.3570
5 17q rs rs Interstitial lung disease MAPT 17q rs rs Progressive supranuclear palsy MAPT 17q rs rs Parkinson s disease MAPT 17q rs rs Intracranial volume MAPT, GRN, 15q rs rs Aortic root size LOXL1 6q rs rs Height BCKDHB 21q rs rs Height KCNE2 21q rs rs Body mass index (interaction) LOC , KCNE2 15q rs rs Keloid NEDD4 8p rs rs Myopia (pathological) Intergenic 2p rs rs Sex hormone binding globulin levels LHCGR 2p rs rs Height EFEMP1 2p rs rs Height EFEMP1 2p rs rs Height EFEMP1, PNPT1 2p rs rs Height EFEMP1 2p rs rs Height EFEMP1 2p rs rs Height EFEMP1 2p rs rs Height EFEMP1 2p rs rs Height EFEMP1 4p rs rs Obesity related traits CC2D2A Replication of GWAS Catalog Results The following table shows, for each GWAS Catalog result for similar traits, our association test result for our best available proxy (distance < 100kb, r 2 > 0.8). no relevant GWAS catalog terms were available Nearby Nonsynonymous SNPs region position our.name our.pval dist rsqr assay.name gene aa.chg 20q rs rs UQCC R51Q 20q rs rs GDF5 S276A 6q rs rs FNDC1 P122S 6q rs rs FNDC1 E463Q 6q rs rs FNDC1 Q1003E 6q rs rs FNDC1 D1180E 6q rs rs FNDC1 L1261P 6q rs rs FNDC1 Q1280R 6q rs rs FNDC1 T1504K 6p rs rs NOTCH4 T320A 16q rs rs CTU2 V332I 16q rs rs CTU2 R427Q 16q rs rs PIEZO1?749? 16q rs rs PIEZO1 R720H 17q rs rs ARHGAP27 A117T 17q rs rs SPPL2C S224P 17q rs rs SPPL2C A332T 17q rs rs SPPL2C R461P 17q rs rs SPPL2C I471V 17q rs rs SPPL2C S601P 17q rs rs SPPL2C G620R 17q rs rs SPPL2C P643R 17q rs rs SPPL2C H649H 17q rs rs SPPL2C Q653Q 17q rs rs MAPT P202L 17q rs rs MAPT D285N 17q rs rs MAPT V289A 17q rs rs MAPT R370W 17q rs rs MAPT S447P 17q rs rs MAPT?1735? 17q rs rs KANSL1?1225? 17q rs rs KANSL1 I1085T 17q rs rs KANSL1 F917F 17q rs rs KANSL1 D914D 17q rs rs KANSL1 S718P 17q rs rs KANSL1 N225D 17q rs rs KANSL1 K104T 15q rs rs LOXL1 R141L 5q rs rs VCAN K349E Nearby Expression QTLs region position our.name our.pval dist rsqr assay.name eqtl.dist eqtl.gene eqtl.pval eqtl.rsqr tissue pubmed.id Nature Genetics: doi: /ng.3570
6 20q rs rs CPNE B Cell q rs rs CPNE Monocyte q rs rs UQCC Monocyte q rs rs UQCC Monocyte p rs rs BAT Monocyte q rs rs SEPT Lymphoblastoid q rs rs FAM38A Monocyte q rs rs MGC B Cell q rs rs LRRC37A Monocyte q rs rs MGC Monocyte q rs rs HS B Cell q rs rs C17ORF B Cell q rs rs NMT Lymphoblastoid q rs rs KANSL Lymphoblastoid q rs rs NSF Lymphoblastoid q rs rs GOSR Lymphoblastoid q rs rs CRHR Lymphoblastoid q rs rs LCA Fibroblast q rs rs C21ORF B Cell p rs rs FDFT Monocyte p rs rs BLK Monocyte p rs rs C8ORF Monocyte p rs rs MFHAS B Cell p rs rs C8orf Lymphoblastoid p rs rs PPP1R3B Lymphoblastoid p rs rs CLDN Monocyte p rs rs DEFA B Cell p rs rs MFHAS B Cell p rs rs MFHAS Monocyte p rs rs EPS Lymphoblastoid p rs rs KTI B Cell p rs rs GPX Monocyte p rs rs ELAC B Cell Nearby Clinical Variants source region our.name our.pval dist rsqr assay.name gene phenotype accession clinvar 15q24.1 rs rs LOXL1 Pseudoexfoliation glaucoma SNOMED CT clinvar 6q14.1 rs rs BCKDHB Maple syrup urine disease Office of Rare Diseases3228 clinvar 6q14.1 rs rs BCKDHB Maple syrup urine disease SNOMED CT clinvar 6q14.1 rs rs BCKDHB Maple syrup urine disease type 1B Office of Rare Diseases8597 clinvar 6q14.1 rs rs BCKDHB Maple syrup urine disease Office of Rare Diseases3228 clinvar 6q14.1 rs rs BCKDHB Maple syrup urine disease SNOMED CT clinvar 6q14.1 rs rs BCKDHB Maple syrup urine disease type 1B Office of Rare Diseases8597 Regional Association Plots Nature Genetics: doi: /ng.3570
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