Limb development genes underlie variation in human fingerprint patterns

• Published in: Cell Vol. 185; no. 1; pp. 95 - 112.e18
• Main Authors: Li, Jinxi, Glover, James D., Zhang, Haiguo, Peng, Meifang, Tan, Jingze, Mallick, Chandana Basu, Hou, Dan, Yang, Yajun, Wu, Sijie, Liu, Yu, Peng, Qianqian, Zheng, Shijie C., Crosse, Edie I., Medvinsky, Alexander, Anderson, Richard A., Brown, Helen, Yuan, Ziyu, Zhou, Shen, Xu, Yanqing, Kemp, John P., Ho, Yvonne Y.W., Loesch, Danuta Z., Wang, Lizhong, Li, Yingxiang, Tang, Senwei, Wu, Xiaoli, Walters, Robin G., Lin, Kuang, Meng, Ruogu, Lv, Jun, Chernus, Jonathan M., Neiswanger, Katherine, Feingold, Eleanor, Evans, David M., Medland, Sarah E., Martin, Nicholas G., Weinberg, Seth M., Marazita, Mary L., Chen, Gang, Chen, Zhengming, Zhou, Yong, Cheeseman, Michael, Wang, Lan, Jin, Li, Headon, Denis J., Wang, Sijia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06-01-2022; Cell Press
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Asians - genetics; Body Patterning - genetics; Child; Cohort Studies; Dermatoglyphics; EVI1; Female; fingerprint pattern; Fingers - growth & development; Forelimb - growth & development; Genetic Loci; genetics; Genome-Wide Association Study; Humans; limb development; Male; MDS1 and EVI1 Complex Locus Protein - genetics; Mice; Middle Aged; Organogenesis - genetics; Polymorphism, Single Nucleotide; Toes - growth & development; trans-ethnic meta-analysis; Young Adult; limb development; EVI1; fingerprint pattern; genetics; trans-ethnic meta-analysis; genome-wide association study
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2021.12.008

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.
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•GWAS identifies variants associated with fingerprint type across all digits•Fingerprint-associated genes are strongly enriched for limb development functions•Evi1 alters dermatoglyphs in mice by modulating limb rather than skin development•Fingerprint patterns are genetically correlated with hand and finger proportions
Genome-wide association scans in Han Chinese individuals and a trans-ethnic meta-analysis reveal genetic regions that are associated with specific fingerprint patterning; functional studies in mouse models confirm a role of EVI1 in early limb development and ridge patterning.