Abstract
Fingerprints are of long-standing practical and cultural interest, but little is known about the mechanisms that underlie their variation. Using genome-wide scans in Han Chinese cohorts, we identified 18 loci associated with fingerprint type across the digits, including a genetic basis for the long-recognized “pattern-block” correlations among the middle three digits. In particular, we identified a variant near EVI1 that alters regulatory activity and established a role for EVI1 in dermatoglyph patterning in mice. Dynamic EVI1 expression during human development supports its role in shaping the limbs and digits, rather than influencing skin patterning directly. Trans-ethnic meta-analysis identified 43 fingerprint-associated loci, with nearby genes being strongly enriched for general limb development pathways. We also found that fingerprint patterns were genetically correlated with hand proportions. Taken together, these findings support the key role of limb development genes in influencing the outcome of fingerprint patterning.
| Original language | English |
|---|---|
| Article number | E18 |
| Pages (from-to) | P95-112 |
| Journal | Cell |
| Volume | 185 |
| Issue number | 1 |
| Early online date | 6 Jan 2022 |
| DOIs | |
| Publication status | E-pub ahead of print - 6 Jan 2022 |
Bibliographical note
Funding Information:We would like to thank the participants of the TZL, NSPT, JD, CKB, WeGene, ALSPAC, QIMR, and Pittsburgh study who consented to participate in research, and the whole TZL, NSPT, and JD teams, which include interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. We also thank F.W. for her help with Figure 1 A and W.S. for her help with graphic abstract. We thank Dida Biotech for performing the Luciferase assay experiments. This project was funded by the “Strategic Priority Research Program” of the Chinese Academy of Sciences ( XDB38020400 to S. Wang); Science and Tecnology Commission of Shanghai Municipality; the Ministry of Science and Technology of the People's Republic of China; Shanghai Municipal Science and Technology Major Project ( 2017SHZDZX01 to L.J. and S. Wang); National Key Research and Development Project ( 2018YFC0910403 to S. Wang); Max Planck-CAS Paul Gerson Unna Independent Research Group Leadership Award (to S. Wang); National Natural Science Foundation of China (NSFC) ( 31521003 to L.J., 81622003 to L.W., 81373082 to J. Lv, and 31771325 to J.T.); China Postdoctoral Science Foundation ( 2019M651351 to J. Li); National Science & Technology Basic Research Project ( 2015FY111700 to L.J.); CAMS Innovation Fund for Medical Sciences ( 2019-I2M-5-066 to L.J.); The 111 Project ( B13016 to L.J.); Major Research Program of National Natural Science Foundation of China ( 91731303 to J.T.); the National Institute for Dental and Craniofacial Research (NIDCR) ( R01-DE016148 to M.L.M and S.M.W and R21-DE016930 to M.L.M); Biotechnology and Biological Sciences Research Council ( BBS/E/D/10002071 and BB/T007788/1 to D.J.H.); MRC ( G1100357 to R.A.A and MR/N022556/1 [MRC Centre for Reproductive Health]; European Commission; Marie Sklodowska-Curie Actions Individual fellowship 706429 ; Wellcome Trust/DBT India Alliance Early Career Fellowship ( IA/E/18/1/504338 to C.B.M); Australian Research Council ( A7960034 , A79906588 , A79801419 , DP0212016 , and DP0343921 to S.E.M); Australian National Health and Medical Research Council (NHMRC) ( 241944 , 339462 , 389927 , 389875 , 389891 , 389892 , 389938 , 443036 , 442915 , 442981 , 496739 , 552485 , and 552498 to S.E.M); the UK Medical Research Council ; the Wellcome Trust ( 102215/2/13/2 ); the University of Bristol ; Medical Research Council ( MC_UU_12013/4 to D.M.E. and MC_UU_12013/3 to N.J.T.); Australian Research Council Future Fellowship ( FT130101709 to D.M.E.); the Hong Kong Kadoorie Charitable Foundation ; UK Wellcome Trust ( 202922/Z/16/Z , 104085/Z/14/Z , and 088158/Z/09/Z ); UK Medical Research Council ( MC-PC-13049 and MC-PC-14135 ); and core funding to the Clinical Trial Service Unit and Epidemiological Studies Unit at Oxford University from British Heart Foundation , UK MRC , and Cancer Research UK (to R.G.W. and Z.C.). S.E.M. is supported by NHMRC ( SRF 1103623 ).
Funding Information:
We would like to thank the participants of the TZL, NSPT, JD, CKB, WeGene, ALSPAC, QIMR, and Pittsburgh study who consented to participate in research, and the whole TZL, NSPT, and JD teams, which include interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. We also thank F.W. for her help with Figure 1A and W.S. for her help with graphic abstract. We thank Dida Biotech for performing the Luciferase assay experiments. This project was funded by the ?Strategic Priority Research Program? of the Chinese Academy of Sciences (XDB38020400 to S. Wang); Science and Tecnology Commission of Shanghai Municipality; the Ministry of Science and Technology of the People's Republic of China; Shanghai Municipal Science and Technology Major Project (2017SHZDZX01 to L.J. and S. Wang); National Key Research and Development Project (2018YFC0910403 to S. Wang); Max Planck-CAS Paul Gerson Unna Independent Research Group Leadership Award (to S. Wang); National Natural Science Foundation of China (NSFC) (31521003 to L.J. 81622003 to L.W. 81373082 to J. Lv, and 31771325 to J.T.); China Postdoctoral Science Foundation (2019M651351 to J. Li); National Science & Technology Basic Research Project (2015FY111700 to L.J.); CAMS Innovation Fund for Medical Sciences (2019-I2M-5-066 to L.J.); The 111 Project (B13016 to L.J.); Major Research Program of National Natural Science Foundation of China (91731303 to J.T.); the National Institute for Dental and Craniofacial Research (NIDCR) (R01-DE016148 to M.L.M and S.M.W and R21-DE016930 to M.L.M); Biotechnology and Biological Sciences Research Council (BBS/E/D/10002071 and BB/T007788/1 to D.J.H.); MRC (G1100357 to R.A.A and MR/N022556/1 [MRC Centre for Reproductive Health]; European Commission; Marie Sklodowska-Curie Actions Individual fellowship 706429; Wellcome Trust/DBT India Alliance Early Career Fellowship (IA/E/18/1/504338 to C.B.M); Australian Research Council (A7960034, A79906588, A79801419, DP0212016, and DP0343921 to S.E.M); Australian National Health and Medical Research Council (NHMRC) (241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496739, 552485, and 552498 to S.E.M); the UK Medical Research Council; the Wellcome Trust (102215/2/13/2); the University of Bristol; Medical Research Council (MC_UU_12013/4 to D.M.E. and MC_UU_12013/3 to N.J.T.); Australian Research Council Future Fellowship (FT130101709 to D.M.E.); the Hong Kong Kadoorie Charitable Foundation; UK Wellcome Trust (202922/Z/16/Z, 104085/Z/14/Z, and 088158/Z/09/Z); UK Medical Research Council (MC-PC-13049 and MC-PC-14135); and core funding to the Clinical Trial Service Unit and Epidemiological Studies Unit at Oxford University from British Heart Foundation, UK MRC, and Cancer Research UK (to R.G.W. and Z.C.). S.E.M. is supported by NHMRC (SRF 1103623). S. Wang, D.J.H. and L.J. conceived the project and provided main resources. For the discovery, GWAS, H.Z. J. Li, J.T. Y.Y. S.Z. J.Z. H.Y. and W.Z. performed data and sample collections. H.Z. J. Li, S.Z. and Y.X. contributed to generating the fingerprint and hand phenotype data. S. Wu, Y. Liu, and Q.P. contributed to generating the SNP array data. J. Li and M.P. performed computational analysis. For the replication and meta-analysis, J. Lv, R.M. R.G.W. K.L. and Z.C. performed data analysis and provided summary statistics results and relevant descriptions for the CKB cohort; Lizhong Wang, Y. Li, S.T. X.W. and G.C. performed data analysis and provided summary statistics results and relevant descriptions for the WeGene cohort; D.M.E. and J.P.K. performed data analysis and provided summary statistics results and relevant descriptions for the ALSPAC; S.E.M. N.G.M. Y.Y.W.H. and D.Z.L. performed data analysis and provided summary statistics results and relevant descriptions for the QIMR; and J.M.C. K.N. E.F. S.M.W. and M.L.M. performed data analysis and provided summary statistics results and relevant descriptions for the Pittsburg cohort. J.L. and M.P. performed the overall analysis. For the functional experiments, D.J.H. J.D.G. C.B.M. and M.C. performed the experiments on mouse models and D.J.H. J.D.G. A.M. R.A.A. and E.I.C. did the gene and protein expression. H.B. aided in data analysis from mouse models. D.H. and Lan Wang performed the luciferase reporter assay. J. Li, D.J.H. and S. Wang wrote the manuscript with input from J.M.C. E.F. S.M.W. M.L.M. M.C. S.E.M. and other co-authors. Lizhong Wang, Y. Li, S.T. X.W. and G.C. are employees of WeGene Inc. The other authors declare no competing interests. We worked to ensure gender balance in the recruitment of human subjects. We worked to ensure sex balance in the selection of non-human subjects. We worked to ensure ethnic or other types of diversity in the recruitment of human subjects. The author list of this paper includes contributors from the location where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.
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