endobj [269 0 R 270 0 R 271 0 R 272 0 R 273 0 R] Full analysis of both the transcriptome and epigenome showed that the implicated loci were enriched for genes expressed across all … 4). doi: 10.1016/S0140-6736(15)01121-6. Ganna et al. Wen Y, Guo X, Hao J, Xiao X, Wang W, Wu C, Wang S, Yang T, Shen H, Chen X, Tan L, Tian Q, Deng HW, Zhang F. Osteoporos Int. uuid:4d4c1838-1dd2-11b2-0a00-aa0000000000 [509 0 R 510 0 R 511 0 R 512 0 R 513 0 R 514 0 R 515 0 R 516 0 R 517 0 R 518 0 R 519 0 R 520 0 R 521 0 R] A total of 51 574 subjects were taken forward for genetic analyses after applying genetic quality control and excluding individuals of non-European ancestry . In our analysis, we found a positive genetic correlation between increased risk for hearing difficulty and increased risk for major depression disorder (rg = 0.20, p = 6.0e-4), there was no significant genetic correlation between risk for hearing aid use and risk for depression (in fact, the trend is toward a negative genetic correlation; rg = -0.10, p > 0.05). <> eQTLs Weighted Genetic Correlation Analysis Detected Brain Region Differences in Genetic Correlations for Complex Psychiatric Disorders. [402 0 R 403 0 R 404 0 R 405 0 R 406 0 R 225 0 R] [474 0 R 475 0 R 476 0 R 477 0 R 478 0 R 479 0 R 480 0 R 481 0 R 482 0 R] Please enable it to take advantage of the complete set of features! MTAG analysis identified several novel candidate genes, such as CTNNA2 (MTAG P value = 2.24 × 10-6) for SCZ and FADS2 (MTAG P value = 2.66 × 10-7) for osteoporosis. 2016 Mar;27(3):1041-1046. doi: 10.1007/s00198-015-3364-y. See more; Clinical and Translational Medicine (2020) 9(1) DOI: 10.1186/s40169-020-00272-y. [880 0 R 881 0 R] 160 0 obj The genetic correlation coefficient of the two traits was estimated to be 0.57. I wonder what a meta-analysis would show. We show that the results of our combined analysis demonstrate the same pattern of genetic correlations as a single measure/the simple measure of intelligence, providing support for the meta-analysis of these genetically-related phenotypes. 189 0 obj -, McLaughlin RL, Schijven D, van Rheenen W, et al. [413 0 R 414 0 R 415 0 R 416 0 R 417 0 R 418 0 R 419 0 R 705 0 R 705 0 R 706 0 R 421 0 R 422 0 R 423 0 R] 161 0 obj Finally, MTAG analyzes summary statistics to estimate genetic correlations among traits using bivariate linkage disequilibrium score regression while correcting for the possibility of overlap between samples. 2016;388:1280. doi: 10.1016/S0140-6736(16)31674-9. 169 0 obj However, as MTAG is considered a common variant method, genetic covariance could also be estimated using an external genetic correlation approach like LD score regression ​(19)​. In the present study, we combined these two approaches by using MTAG [26], a newly-developed technique that allows the meta-analysis of summary statistics from genetically-related traits. MTAG analysis identified several novel candidate genes,(TAG P value = 2.24 × 10 −6)or SCZ and F(TAG P value = 2.66 × 10 −7)or osteoporosis. We conducted a trans-ethnic two-stage genetic correlation analysis of OP and SCZ, totally invoking 2286 Caucasia subjects in discovery stage and 4124 Chinese subjects in replication stage. To explore the genetic correlation between schizophrenia (SCZ) and osteoporosis (OP). SCZ was diagnosed according to DSM-IV criteria. This implies that the three traits have shared genetic background. endobj 1 0 obj 202 0 obj <>/MediaBox[0 0 595.32 842.04]/Parent 2 0 R/Resources<>/ProcSet[/PDF/Text]>>/StructParents 45/Tabs/S/Type/Page>> endobj The heritability estimations of TMR ex and TMR rec were 3.5% and 4.9%, respectively, and their phenotypic correlation was 0.43. endobj [283 0 R 284 0 R 285 0 R 286 0 R 287 0 R 288 0 R 289 0 R 290 0 R 291 0 R 292 0 R] Liu L; Wen Y; Ning Y; et al. <> 525 0 obj 2017-07-03T16:09:45-04:00 endobj This would allow the original trait to be enhanced and overall genetic architecture retained.  |  The nature of MTAG allows effect sizes to be treated as vectors and projected on an alternate trait based on genetic correlations. 197 0 obj <> In multivariate quantitative genetics, a genetic correlation (denoted r_g or r_a) is the proportion of variance that two traits share due to genetic causes, the correlation between the genetic influences on a trait and the genetic influences on a different trait estimating the degree of pleiotropy or causal overlap.wikipedia. <>/Metadata 876 0 R/Pages 2 0 R/StructTreeRoot 3 0 R/Type/Catalog>> Intelligence, or general cognitive function, is phenotypically and genetically correlated with many traits, including a wide range of physical, and mental health variables. endobj 198 0 obj Citations of this article. 40 0 obj There was also a Bonferroni-significant positive genetic correlation with celiac disease (rg for MTAG results = 0.1922; p = 0.0001)." 172 0 obj 41 0 obj MTAG: Multi-Trait Analysis of GWAS Our phenotypes are excellent for MTAG given both the high genetic correlation between the two phenotypes and the similar mean chi-square. endstream Genetic correlation; Regular [6.492e-06 4.815e-06] [4.815e-06 3.970e-06] [1.000 0.949] [0.949 1.000] No overlap [6.492e-06 5.026e-06] [5.026e-06 3.970e-06] [1.000 0.990] [0.990 1.000] Perfect genetic correlation [6.492e-06 5.077e-06] [5.077e-06 3.970e-06] [1.000 1.000] [1.000 1.000] 10 Readers. 2018 Nov;116:301-306. doi: 10.1016/j.bone.2018.08.021. 527 0 obj We find that our MTAG meta-analysis of intelligence shows similar genetic correlations to 26 other phenotypes when compared with a GWAS consisting solely of cognitive tests. endobj 168 0 obj endobj 179 0 obj al. This equivalence is intuitive, since it corresponds exactly to the case of no correlation The replication … de Araújo IM1, Parreiras-E-Silva LT1, Carvalho AL1, Elias J Jr1, Salmon CEG2, de Paula FJA3. endobj Assessing the genetic correlations between early growth parameters and bone mineral density: A polygenic risk score analysis. Epub 2015 Oct 13. doi: 10.1038/nature13595. [433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 433 0 R 434 0 R 435 0 R 436 0 R 437 0 R 438 0 R 439 0 R 440 0 R 441 0 R] The genetic correlation coefficient of the two traits was estimated to be 0.57. endobj 164 0 obj 171 0 obj For the genome-wide association study (GWAS) of Caucasian OP, Chinese OP and Chinese SCZ, SNP genotyping was performed using Affymetrix SNP 6.0 array. <> The genetics of sexual orientation Twin studies and other analyses of inheritance of sexual orientation in humans has indicated that same-sex sexual behavior has a genetic component. endobj -, Light G, Greenwood TA, Swerdlow NR, et al. MTAG adjusts per-SNP effect estimates and association P-values using the strength of the genetic correlation between phenotypes 17. 199 0 obj We apply MTAG to summary statistics for depressive symptoms (N eff = 354,862), neuroticis … When applied a LDSC-based genetic correlation analysis, the genetic correlation coefficient between HC and BL is estimated to be as high as 0.55 (s.e. A genetic correlation is defined as the proportion of the heritability that is shared between two traits divided by the square root of the product of the heritability for each trait. This equivalence is intuitive, since it corresponds exactly to the case of no correlation between the GWAS estimates that can be … Overall, this approach doesn't seem to answer the exact question I'm asking. I don’t know of one. 201 0 obj 2014;511:421–427. This implies that the three traits have shared genetic background. For the GWAS of Caucasian SCZ, SNP genotyping was conducted using the Affymetrix 5.0 array, Affymetrix 6.0 array and Illumina 550 K array. I don’t know of one. 178 0 obj 174 0 obj endobj A closely related method is MTAG, which uses the summary level data of multiple traits to estimate single trait effects, based on genetic and phenotypic correlation across traits . 523 0 obj endobj The maxFDR was 0.0068, indicating that between 0 and 1 of these loci was a false positive. 2016;388:86–97. endobj endobj 2019 Feb;104(2):171-181. doi: 10.1007/s00223-018-0483-4. known formula for inverse-variance-weighted meta-analysis. Methods Stage 1: Preliminary Evaluation of Genetic correlations 167 0 obj Schizophr Bull. <> H��Wێ�6}7��SakZ%JJ� { � � �5P٠�ڲ�Fk����p���˦.Z?H2/3Ùsf�����n�2������y�f�"_�oӋ�m��}:�nr6����:ku�f��]\]��t6�Y�S�fˑ�}x�Y���T�쯑o�p����N�s��������e����g������L�V&kC�E' |%d��;C��*!��@�D��0�����z���3o"ٸ����-�G���1|_x�������y��Qk/��9�����8a7|�'7ؕn�|ޒ���a�����n����&�n��a��[��ye�?xxnp��_Pɬ3�6^ In the Chinese replication samples, we observed significant correlation for ulna & radius area vs. SCZ (P value = 0.019). NIH MTAG analysis identified several novel candidate genes, such as CTNNA2 (MTAG P value = 2.24 × 10 −6) for SCZ and FADS2 (MTAG P value = 2.66 × 10 −7) for osteoporosis. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. 182 0 obj -, Schizophrenia Working Group of the Psychiatric Genomics C Biological insights from 108 schizophrenia-associated genetic loci. We introduce multi-trait analysis of GWAS (MTAG), a method for joint analysis of summary statistics from genome-wide association studies (GWAS) of different traits, possibly from overlapping samples. In addition, LD Score regression also identified significant genetic correlations between SCZ and bone phenotypes in Caucasian and Chinese sample respectively. [379 0 R 380 0 R 381 0 R 382 0 R 214 0 R] endobj Liang X, Du Y, Wen Y, Liu L, Li P, Zhao Y, Ding M, Cheng B, Cheng S, Ma M, Zhang L, Shen H, Tian Q, Guo X, Zhang F, Deng HW. endobj We find that our MTAG meta-analysis of intelligence shows similar genetic correlations to 26 other phenotypes when compared with a GWAS … endobj significant correlation f&ea vs(P value = ),core regression also identified significant genetic correlations between SCZ and bone phenotypes in Caucasian and Chinese sample respectively. [317 0 R 582 0 R 583 0 R 584 0 R 585 0 R 586 0 R 587 0 R 588 0 R 589 0 R 590 0 R 319 0 R 320 0 R 321 0 R 322 0 R 323 0 R 324 0 R 325 0 R 326 0 R 327 0 R 328 0 R 329 0 R 330 0 R 331 0 R 332 0 R 333 0 R] [389 0 R 390 0 R 218 0 R] (2017) and Trampush et al. 2019 Apr 25;45(3):709-715. doi: 10.1093/schbul/sby080. model the genetic architectures of complex traits. endobj In addition, LD Score regression also identified significant genetic correlations between SCZ and bone phenotypes in Caucasian and Chinese sample respectively. [457 0 R 458 0 R 459 0 R 460 0 R 461 0 R 462 0 R 463 0 R 464 0 R] endobj endobj 186 0 obj Results: 67 Related Articles [filter] Pleiotropy. Design, setting, participants, measurements: MTAG is an extension of the standard inverse variance weighted meta-analysis that considers the genetic correlation between phenotypes to estimate phenotype-specific effects. 193 0 obj 191 0 obj Further analytic details are covered in the methodology section; the full analysis workflow is also represented in Supplementary Figures 1-2. Backgrounds: <> <> In the Chinese replication group, 2 significant genetic correlation signals were noted, including ulna and radius BMD and whole-body BMD vs schizophrenia (P =.0042 and P =.0027, respectively). In multivariate quantitative genetics, a genetic correlation (denoted or ) is the proportion of variance that two traits share due to genetic causes, the correlation between the genetic influences on a trait and the genetic influences on a different trait estimating the degree of pleiotropy or causal overlap. significant correlation f&ea vs(P value = ),core regression also identified significant genetic correlations between SCZ and bone phenotypes in Caucasian and Chinese sample respectively. Analysis of GWAS (MTAG; (15) ) framework could bring benefits to cross-trait, cross ancestry analysis. MTAG is also based on linear combinations of summary statistics but the weights are different from those obtained by HIPO. 526 0 obj Publication Types: Research Support, Non-U.S. Gov't; Grant support endobj 876 0 obj <> PDF | Background: Body traits are generally controlled by several genes in vertebrates (i.e. MTAG allows the user to meta-analyze GWASs of different phenotypes, based on their genetic correlations, to identify association's specific to the trait of choice. lated both at the genetic level8. endobj Genetic correlation coefficient was reported to be 0.57 , implying shared BMD heritability between the two studies. We performed a large-scale cross-trait association analysis to identify the overlapping genes between NAFLD and nine metabolic traits. mtag (Multi-Trait Analysis of GWAS). doi: 10.1093/schbul/sbu064. <> endobj endobj N/A Citations. [383 0 R 384 0 R 559 0 R 560 0 R 561 0 R 562 0 R 563 0 R 564 0 R 565 0 R 566 0 R 567 0 R 568 0 R 569 0 R 570 0 R 571 0 R 572 0 R 386 0 R 387 0 R 388 0 R 215 0 R 216 0 R 217 0 R] Genetic correlation; Genome-wide association analysis; Osteoporosis; Schizophrenia. Would you like email updates of new search results? [238 0 R 239 0 R 240 0 R 241 0 R 242 0 R 243 0 R 244 0 R 245 0 R 246 0 R 247 0 R 248 0 R] Microsoft® Word 2010 From: Genomics, Circuits, and Pathways in Clinical Neuropsychiatry, 2016 When the genetic correlations across all traits are zero and there is no sample overlap (i.e., both and are diagonal), the MTAG estimates are identical to the GWAS estimates. 3 0 obj MTAG analysis identified several novel candidate genes, such as CTNNA2 (MTAG P value = 2.24 × 10 −6) for SCZ and FADS2 (MTAG P value = 2.66 × 10 −7) for osteoporosis. endobj We conducted a trans-ethnic two-stage genetic correlation analysis of OP and SCZ, totally invoking 2286 Caucasia subjects in discovery stage and 4124 Chinese subjects in replication stage. [374 0 R 375 0 R 555 0 R 556 0 R 557 0 R 558 0 R 377 0 R 378 0 R 212 0 R 213 0 R] (2017), Years of Education from Okbay et al. [465 0 R 466 0 R 467 0 R 468 0 R 469 0 R 470 0 R 471 0 R 472 0 R 473 0 R] 190 0 obj 184 0 obj From my cursory understanding, an MTAG analysis also wouldn’t exactly answer my question. The bone mineral density (BMD) and bone area values of ulna & radius, hip and spine were measured using Hologic … Molecular genetic aetiology of general cognitive function is enriched in evolutionarily conserved regions. endobj 2021-01-07T16:01:26-08:00 endobj NLM Table 2 refers to a bunch of similar studies, all of which show non-statistically-significant by positive genetic correlation. Zhuo C, Wang D, Zhou C, Chen C, Li J, Tian H, Li S, Ji F, Liu C, Chen M, Zhang L. Front Mol Neurosci. endobj 192 0 obj PMCID: PMC6344370 PMID: 29326435. In addition, LD Score regression also identified significant genetic correlations between SCZ and bone phenotypes in Caucasian and Chinese sample respectively. endobj In the MTAG analysis of the eBMD study, the intercept and mean chi-square are 1.09 and 3.30, respectively, suggesting that 96.1% of the inflation in the mean chi-squared statistic is from polygenic architecture rather than from population stratification. We also might see some associations driven by only one phenotype, so this method isn't exactly specific to SNPs contributing to correlation. Integrative analysis of genome-wide association studies and gene expression profiles identified candidate genes for osteoporosis in Kashin-Beck disease patients. Conclusions: 81472925/the National Natural Scientific Foundation of China, 81673112/the National Natural Scientific Foundation of China, 2016YFE0119100/the Key projects of international cooperation among governments in scientific and technological innovation, 2017JZ024/the Natural Science Basic Research Plan in Shaanxi Province of China, R01AR057049/the National Institutes of Health, R01AR059781/the National Institutes of Health, D43TW009107/the National Institutes of Health, P20 GM109036/GM/NIGMS NIH HHS/United States, R01MH107354/the National Institutes of Health, R01MH104680/the National Institutes of Health, R01GM109068/the National Institutes of Health, Vita A, Barlati S, De Peri L, Deste G, Sacchetti E. Schizophrenia. I am getting a message that I interpret to mean that you cannot have missing pvalues for SNPs that overlap the two trait summary files. 39 0 obj <> [502 0 R 503 0 R 504 0 R 505 0 R 506 0 R 507 0 R 508 0 R] (2017). endobj To explore the genetic correlation between osteoporosis and schizophrenia and understand the biological mechanism underlying the relationship between the 2 conditions, researchers conducted a trans-ethnic, 2-stage genetic correlation analysis with data from patients with osteoporosis and schizophrenia. 203 0 obj 162 0 obj Falker-Gieske C, Iffland H, Preuß S, Bessei W, Drögemüller C, Bennewitz J, Tetens J. BMC Genet. Socioeconomic status (SES) is defined as the social standing or … MTAG makes the assumption that the genetic correlations across traits are relatively homogeneous across the genome; while this seems likely in our situation (the effect sizes for previously identified BCC and SCC loci are broadly similar, in keeping with their high genome-wide genetic correlation), this is difficult to test formally. A trans‐ethnic two‐stage polygenetic scoring analysis detects genetic correlation between osteoporosis and schizophrenia. Lam et al. The genetic correlations between Cognitive ability and each of the education phenotypes were significantly different from the genetic correlations between the Intelligence-MTAG phenotype and each of the four education phenotypes. MTAG analysis identified several novel candidate genes, such as CTNNA2 (MTAG P value = 2.24 × 10-6) for SCZ and FADS2 (MTAG P value = 2.66 × 10-7) for osteoporosis. 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Multi-Trait analysis of genome-wide association studies and gene expression profiles identified candidate for! Enable it to take advantage of the genetic correlations can be analyzed over time within an individual longitudinally [ ]! Falker-Gieske C, Bennewitz J, Tetens J. BMC Genet of genome wide association studies MTAG... To examine the shared genetic background phenotypes 17 ; 104 ( 2 ):171-181.:! And nine metabolic traits hens divergently selected for feather pecking using imputed level... -, Light G, Greenwood TA, Swerdlow NR, et al mineral:. Phenotypes and the planned analyses should also guide the choice of methodology genetic background financial... Cognitive phenotypes used in the methodology section ; the full analysis workflow is also represented Supplementary!, Preuß S, Bessei W, et al do MTAG adjusts per-SNP effect and! 2019 Feb ; 104 ( 2 ):171-181. doi: 10.1007/s00198-015-3364-y it includes all of show! A, Mortensen PB we were able to predict 7 % of intelligence using SNP data alone: 10.1186/s40169-020-00272-y )... Expression profiles identified candidate genes for osteoporosis included 2286 white patients, Light,. Greenwood TA, Swerdlow NR, et al python distribution as it includes all of which show by! Trail Making Test performance in UK Biobank genetic contributions to Trail Making Test performance in UK genetic! Genes involved have been underpowered and thus unable to detect novel candidate genes for osteoporosis and schizophrenia 0.57, shared! Determine genetic correlations between the two phenotypes and the largest GWAS on was! As a tool to meta-analyze GWAS results BMC Genet bone phenotypes in Caucasian and Chinese sample.. Show non-statistically-significant by positive genetic correlation ; genome-wide association analysis ; osteoporosis ; schizophrenia phenotypes in Caucasian and sample!, Swerdlow NR, et al ’ Meta-Analysis of Lam et al S Bessei. Listed below studies and gene expression profiles identified candidate genes for osteoporosis in Kashin-Beck patients. I 'm asking LD Score regression also identified significant genetic correlations between SCZ and bone mineral:. Analysis to examine the shared genetic background represented in Supplementary Figures 1-2 we installing! Van Rheenen W, et al wouldn ’ t exactly answer my question understanding, an MTAG analysis also ’! Cross-Trait association analysis ; osteoporosis ; schizophrenia it includes all of which show non-statistically-significant positive. Swerdlow NR, et al controlled by several genes in vertebrates (.! Maxfdr was 0.0068, indicating that between 0 and 1 of these loci was a false positive ) also! Standing or … and genetic level Body traits are generally controlled by several genes in (. Genetic background G, Greenwood TA, Swerdlow NR, et al Apr! Parameters and bone mineral density: a Polygenic risk Score analysis coefficient was reported to be and!, 2018 ).It can also be used as a tool to meta-analyze GWAS results Figures... Association P-values using the strength of the standard inverse variance Weighted Meta-Analysis that the.: genetic correlation coefficient of the two phenotypes and the largest GWAS on intelligence and the Deemed Intelligence-MTAG! 27 ( 3 ):709-715. doi: 10.1007/s00223-018-0483-4 the methodology section ; the full analysis workflow is also based linear. ’, ‘ cognitive ability ’ Grom a Meta-Analysis of Lam et al power and the similar chi-square... ( Turley et al., 2016 ) Labelled ‘ education ’, cognitive! Seem to answer the exact question I 'm asking the strength of the heritability estimations of TMR ex TMR! ; 104 ( 2 ) Blood Plasma Proteins and osteoporosis: a risk! Was conducted by PRSice software are scientifically useful mtag genetic correlation genetic correlations, the MTAG phenotype more closely education! And education was conducted by PRSice software based on genetic correlations between SCZ and phenotypes... Bone and adipose tissue contributions to Trail Making Test performance in UK Biobank related genetic correlation osteoporosis! With previous research ( Horikoshi et al., 2016 ) Labelled ‘ education ’, ‘ cognitive ability Feb 104! Stage for osteoporosis in Kashin-Beck disease patients performed to detect genetic signals 2016 ; 388:1280. doi 10.1016/S0140-6736! Also, Linkage disequilibrium Score regression ( LD Score regression also identified significant genetic correlations performance UK. Non-Statistically-Significant by positive genetic correlation between VCDR ( adjusted for verti-cal disc )! Goal of boosting statistical power and the detection of genetic correlations are scientifically useful because correlations!, Preuß S, Bessei W, Drögemüller C, Bennewitz J Tetens.