Normal facial development is dependent on Cranial Neural Crest Cells and correctly spatially positioned and differentiated tissues and structures that influence the shape and morphological features of the face. A. 37, 6271. J. Hum. Many of the previously discussed genetic variants associated with facial traits in GWAS reside in non-protein coding regions of the genome with unclear functional relevance. BMJ Open 7:e015410. usually an angry face with an open gorilla mouth. Aspinall, A., Raj, S., Jugessur, A., Marazita, M., Savarirayan, R., and Kilpatrick, N. (2014). Comparison of three-dimensional surface-imaging systems. Dev. doi: 10.3390/ijerph10115953. Eur. Nature 414, 909912. In particular, the strong effects that genetic variation can have on facial appearance are highlighted by historical portraits of the European royal family, the Habsburgs (14381740). Anthropol. doi: 10.1098/rspb.2000.1327, Little, A. C., Penton-Voak, I. S., Burt, D. M., and Perrett, D. I. Stability and flexibility of epigenetic gene regulation in mammalian development. 13, 105108; discussion 109110. (2018). Am. (2013). Focusing on specific phenotypes and genetic variants in families will identify additional rare variants should be followed-up with a combination of genotyping and deep re-sequencing of the variants or genes of interest in large numbers of cases and controls. Orthodont. (2017). The PAX3 gene is associated with the distance between the mid-endocanthion point and surface nasion with a mean distance of 17.5 mm with differing axis values up to 6.7 mm (x), 17.7 mm (y), and 18.9 mm (z). The maternal environment is thought to play an important role with regards to orofacial clefts. 468, 959969. Genet. 6. Med. doi: 10.1371/journal.pone.0162250, Evans, D. M. (2018). Nose shape and climate. 24, 579589. Long-range enhancers regulating Myc expression are required for normal facial morphogenesis. This is where the Scottish and Irish kilts differ the most, as the tartan in which the kilts are made have very different origins and meanings. With increased sample sizes, improved understanding of shared genetic influences on human traits and advancement in techniques there is likely to be significant further progress in the next 6 years. (2014). doi: 10.1016/j.bjps.2014.01.003, Uslu, V. V., Petretich, M., Ruf, S., Langenfeld, K., Fonseca, N. A., Marioni, J.C., et al. First all-in-one diagnostic tool for DNA intelligence: genome-wide inference of biogeographic ancestry, appearance, relatedness, and sex with the Identitas v1 Forensic Chip. The athletic heroes were replaced by young Irish men of lean build and medium height. eds G. J. Huang, R. S., K.W.L. Clin. AJNR Am. Hum. J. Orthod. There has been significant progress in the first 6 years of GWAS and facial genetics. 38, 493502. Facial phenotypes can influence mate choice and be under selection pressures. doi: 10.1136/adc.41.220.613. However, previous studies investigating gene-smoking interactions in the etiology of birth defects have produced mixed results (Shi et al., 2008). WebIrish Ceili Dancing. Vig (Hoboken, NJ: Wiley-Blackwell). Previous epigenome-wide association studies (EWAS) have found evidence of differential DNA methylation between cleft cases and controls (Alvizi et al., 2017), as well as between the different orofacial cleft subtypes (Sharp et al., 2017) implicating the relevance of DNA methylation in craniofacial development. doi: 10.1111/j.1601-6343.2008.00428.x, Toma, A. M., Zhurov, A. I., Playle, R., Marshall, D., Rosin, P. L., and Richmond, S. (2012). SR, ES, LH, and SL highlighted the shared facial traits. The determination of facial appearance, health history and future health risk from DNA is has great potential (Claes et al., 2014; Kayser, 2015; Toom et al., 2016) but caution should be expressed with respect to assumptions, interpretation and individual confidentiality as there is a significant threat to an individual in obtaining healthcare insurance (Hallgrimsson et al., 2014; Idemyor, 2014; Toom et al., 2016). 12, 271281. 36, 506511. Hum. Genet. - Disentangling the environmental factors and relative parental biological contributions to heritable traits can help to answer the age-old question why we look the way that we do?. doi: 10.1093/hmg/ddt104, Cousminer, D. L., Stergiakouli, E., Berry, D. J., Ang, W., Groen-Blokhuis, M. M., Krner, A., et al. Indeed, a previous study demonstrated that a major risk locus for non-syndromic cleft lip/palate (nsCL/P), in a non-coding interval, is involved in the regulation of gene expression in the developing murine face (Uslu et al., 2014) while another study found some evidence that nsCL/P genetic variants may influence nsCL/P risk via changes in DNA methylation and gene expression (Howe et al., 2018b). (2014). Genet. Surg. B., et al. (2014). (2014). Res. Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty. (2014a). doi: 10.1016/0002-9416(79)90274-4, Biedermann, A., Bozza, S., and Taroni, F. (2015). 3. I. Arch. Semin. Key transcriptional factors (activators or repressors) have been identified indicating extensive activation during early craniofacial development. 396, 159168. doi: 10.1520/JFS2004251, Suttie, M., Wozniak, J. R., Parnell, S. E., Wetherill, L., Mattson, S. N., Sowell, E. R., et al. Information on an individuals facial morphology can have several important clinical and forensic applications; informing patient specific models, improving and reducing the need for extensive surgical interventions for craniofacial anomalies/trauma, prediction/reconstruction of the facial form from skeletal remains, and identification of suspects from DNA (Stephan et al., 2005; De Greef et al., 2006; Wilkinson et al., 2006; Beldie et al., 2010; Popat et al., 2010, 2012; Richmond et al., 2012; Al Ali et al., 2014a; Shrimpton et al., 2014; Farnell et al., 2017; Richmond S. et al., 2018). Shared genetic pathways may influence both normal-range variation in facial morphology and craniofacial anomalies. Aust. Second, when testing causality, epigenetic modifications can vary across the life-course, so it can be difficult to discern the direction of effect between an epigenetic modification and the phenotype. Am. WebIrish-Scots (Scottish Gaelic: ireanneach-Albais) are people in Scotland who have traceable Irish ancestry.Although there has been migration from Ireland (especially Ulster) to Britain for millennia permanently changing the historic landscape of Scotland forever, Irish migration to Scotland increased in the nineteenth century, and was highest following the Abbas, H., Hicks, Y., Marshall, D., Zhurov, A. I., and Richmond, S. (2018). bioRxiv. The pattern of facial skeletal growth and its relationship to various common indexes of maturation. (2013). 415, 171187. Pflugers. It is therefore important to use causal inference techniques such as epigenetic Mendelian randomization Relton and Davey Smith, 2012) or the Steiger test (Hemani et al., 2017) to orientate the likely directions of effect between phenotypes, epigenetic modifications and gene expression. 281:20141639. doi: 10.1098/rspb.2014.1639, Rachdaoui, N., and Sarkar, D. K. (2014). Scott, I. M., Clark, A. P., Boothroyd, L. G., and Penton-Voak, I. S. (2013). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). 19, 12631269. Science 342:1241006. doi: 10.1126/science.1241006, Barlow, A. J., Bogardi, J. P., Ladher, R., and Francis-West, P. H. (1999). Arch. Sci. In brief: Gaelic in Scottish is pronounced as Gah-Lick whereas it is pronounce as Gai-Lick in Irish. WebLight eyes and brown and blonde hair is the most common. 21, 548553. Genome-wide association meta-analysis of individuals of European ancestry identifies new loci explaining a substantial fraction of hair color variation and heritability. Neurobiol. doi: 10.1111/1467-8721.00190, Freund, M. K., Burch, K., Shi, H., Mancuso, N., Kichaev, G., Garske, K. M., et al. (2006). However, it is important to note that stochastic chance events such as facial trauma, infections, burns, tumors, irradiation and surgical procedures can all have a significant impact on facial development and consequently facial morphology. Sci. B., Manyama, M., Kimwaga, E., Mathayo, J., Larson, J. R., Liberton, D. K., et al. (2014). doi: 10.1016/j.oooo.2016.08.007, Zaidi, A. 24, 286292. Am. Res. (2018). Epigenomics 10, 2742. The developing fetus may be subject to adverse environments at home, in the workplace or through lifestyle activities (smoking, alcohol and drug intake, allergens, paint, pest/weed control, heavy metals, cleaning, body products such as perfumes and creams). Caserta, D., Graziano, A., Lo Monte, G., Bordi, G., and Moscarini, M. (2013). Int. (2009). doi: 10.1002/humu.22054, Heike, C. L., Upson, K., Stuhaug, E., and Weinberg, S. M. (2010). Nature 461, 199205. et al., 2018) with differential DNA methylation, but contrastingly there is no clear evidence for an association between prenatal alcohol exposure and DNA methylation (Sharp et al., 2018). II. Facial morphology refers to a series of many different complex traits, each influenced by genetic and environmental factors. Eur. Another mechanism via which environmental influences can affect facial traits is natural selection, where certain facial traits may have beneficial effects on reproductive fitness. Keywords: 3D imaging, admixture, ancestry, facial variation, geometric morphometrics, facial genetics, facial phenotyping, genetic-environmental influences, Citation: Richmond S, Howe LJ, Lewis S, Stergiakouli E and Zhurov A (2018) Facial Genetics: A Brief Overview. Defining facial shape can be undertaken in different ways but it is important to appreciate that there will be associations with not only with other facial features but also body phenotypes and medical conditions. J. Craniofac Surg. doi: 10.1093/hmg/ddu150, Crouch, D. J. M., Winney, B., Koppen, W. P., Christmas, W. J., Hutnik, K., Day, T., et al. BMJ Open 5:e009027. Investigating the case of human nose shape and climate adaptation. Surg. Scientists have merged dozens of famous faces to create what they call the most beautiful faces in the world. Genet. (2017). J. Med. doi: 10.1111/acer.13820, Tanner, J. M., Whitehouse, R. H., and Takaishi, M. (1966a). (2018). Combined face-brain morphology and associated neurocognitive correlates in fetal alcohol spectrum disorders. doi: 10.1001/jamapediatrics.2017.0778, Munn, L., and Stephan, C. N. (2018). A., Guerin, D. J., Litzky, J. F., Chavan, N. R., et al. Vis. Part A 143, 11431149. Periderm: Life-cycle and function during orofacial and epidermal development. 40, 3642. There were subtle differences between males and females in relation to the relative prominence of the lips, eyes, and nasal bridges including minor facial asymmetries (Toma et al., 2008, 2012; Wilson et al., 2013; Abbas et al., 2018). 47, 928937. 1:0016. (2014). 9:e1003375. Homo 61, 191203. Genetic evidence of assortative mating in humans. Pathol. LH and AZ wrote the section Environmental Influences. 136, 275286. Different genetic models, genotyping and imputation techniques have been employed and the between-study heterogeneity should be considered. J. Craniofac. A Critical Evaluation of Facial Characteristics and Their Association with Antisocial Behaviour and Psychosis. And, linguistically speaking, the fact that Scottish English only developed three centuries ago makes this accent one of the newest accents in the British Isles. Yes. Very different. I thought I was in a foreign country going to Warwick compared to Scots. Us scots have softer faces, wider eyes and foreheads, J. Anat. Res. Lancet 374, 17731785. Disruptions in the fusion of the facial processes may result in complete or partial clefts of the face, lip and/or palate. Schizophrenia working group of the psychiatric genomics consortium, Patterson N, Daly MJ, Price AL, Neale BMLD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Aesthetic. Mol. However they differ in the way these ingredients are used. Mutat. The soft tissue facial variation has been explored in a large Caucasian population of 15-year-old children (2514 females and 2233 males) recruited from the Avon Longitudinal Study of Parents and Children (ALSPAC). doi: 10.1016/S1090-5138(02)00119-8, Liu, F., Van Der Lijn, F., Schurmann, C., Zhu, G., Chakravarty, M. M., Hysi, P. G., et al. Richmond, S. A., Ali, A. M., Beldi, L., Chong, Y. T., Cronin, A., Djordjevic, J., et al. doi: 10.1136/bmjopen-2013-002910, Djordjevic, J., Zhurov, A. I., and Richmond, S. (2016). doi: 10.1016/j.schres.2003.08.003, Hochheiser, H., Aronow, B. J., Artinger, K., Beaty, T. H., Brinkley, J. F., Chai, Y., et al. Ricketts, R. M. (1982). Nature 447:425. doi: 10.1038/nature05918, Relton, C. L., and Davey Smith, G. (2012). Sci. 41, 161176. In addition, the individual facial traits have yielded impressive levels of significance using a relatively small number of subjects (Evans, 2018). Hum. doi: 10.1371/journal.pone.0093442, Lange, S., Shield, K., Koren, G., Rehm, J., and Popova, S. (2014). The development of the face involves a coordinated complex series of embryonic events. Since Scotland appeared in only one of the names, some people wondered what had happened to their Scottish ancestry. Am. Natl. Heritability in the genomics eraconcepts and misconceptions. Other possible benefits that have been explored include: the fitness advantages of hair color (Adhikari et al., 2016; Hysi et al., 2018), nasal shape and climate adaptation (Zaidi et al., 2017) and the benefits of darker skin pigmentation (Wilde et al., 2014; Aelion et al., 2016). Self-perceived attractiveness influences human female preferences for sexual dimorphism and symmetry in male faces. There was also greater asymmetry in the nsCL/P group (LEFTY1, LEFTY2, and SNAI1) (Miller et al., 2014). doi: 10.1002/(SICI)1097-0177(199904)214:4<291::AID-AJA2>3.0.CO;2-E, Beaty, T. H., Murray, J. C., Marazita, M. L., Munger, R. G., Ruczinski, I., Hetmanski, J. (2010). doi: 10.1016/j.fsigen.2018.04.004, Claes, P., Liberton, D. K., Daniels, K., Rosana, K. M., Quillen, E. E., Pearson, L. N., et al. Genet. Sci. doi: 10.1073/pnas.1711125114, Little, A. C., Burt, D. M., Penton-Voak, I. S., and Perrett, D. I. Biol. A genetic atlas of human admixture history. (2016). Nat. Hammond, P., and Suttie, M. (2012). There are over 25,000 registered Scottish tartans. 10:e1004724. 98, 680696. The genes and broad regional associations are shown in Table 2 (ordered by facial feature and chromosome) and Figure 1 (showing facial region). Department of Human Genetics, Faculty of Medicine, KU Leuven, Belgium, Children's Hospital of Philadelphia, United States. 3:e002910. Understanding the face will explain why we look the way we do a range of normality and abnormality that will be useful in healthcare applications and forensic science. Genet. Genet. Received: 06 July 2018; Accepted: 20 September 2018;Published: 16 October 2018. Statistical power and significance testing in large-scalegenetic studies. (2016). doi: 10.1371/journal.pgen.1002932, Mamluk, L., Edwards, H. B., Savovic, J., Leach, V., Jones, T., Moore, T. H. M., et al. Investigating the shared genetics of non-syndromic cleft lip/palate and facial morphology. doi: 10.1016/j.fsigen.2016.01.010, Tsagkrasoulis, D., Hysi, P., Spector, T., and Montana, G. (2017). Polygenic risk scores, LD score regression (to reduce confounding biases Bulik-Sullivan B.K. 14:e1007501. The authors would also like to thank the participants of the various studies undertaken. doi: 10.1073/pnas.1708207114, Danescu, A., Mattson, M., Dool, C., Diewert, V. M., and Richman, J. M. (2015). Peter Forsberg (hockey player) (Notice how his eyes are higher up. doi: 10.1002/ajpa.20424. The collective use of these techniques to identify the various facial features will increase the robustness of linking the DNA to a likely suspect/candidate. With special thanks to Joel. (2016). The role of sonic hedgehog in normal and abnormal craniofacial morphogenesis. There is clearly a place in forensic science to develop a robust diagnostic tool to determine age, ancestry, appearance, relatedness and sex from DNA samples. 19:1192. doi: 10.1038/ejhg.2011.110, Brinkley, J. F., Fisher, S., Harris, M. P., Holmes, G., Hooper, J. E., Jabs, E. W., et al. Age prediction using methylation techniques have indicated a mean absolute deviation of 58 years (Xu et al., 2015; Bocklandt et al., 2011; Hamano et al., 2017). With improving knowledge of the controlling mechanisms for normal and abnormal facial development, it is logical to pursue healthcare strategies in the first instance to prevent craniofacial anomalies arising, with discussion of risks with genetic counseling, possibly future gene therapies and the follow up with minimally invasive or non-surgical, scarless procedures to correct craniofacial anomalies such as cleft lip and palate and control vertical and horizontal growth particularly of the upper and lower jaws and nose. doi: 10.1038/nature08451, Visscher, P. M., Hill, W. G., and Wray, N. R. (2008). Facial surfaces that are captured in supine and prone position often show slight differences (Munn and Stephan, 2018). Orthod. Elucidating the genetics of craniofacial shape. Genetics of cleft lip and palate: syndromic genes contribute to the incidence of non-syndromic clefts. doi: 10.1093/ije/dyg070, Som, P. M., and Naidich, T. P. (2013). Acad. The study determined that Scotland is divided into six clusters of Psychol. The biologic significance of the divine proportion and Fibonacci series. There was reduced facial convexity (SNAI1), obtuse nasolabial angles, more protrusive chins (SNAI1, IRF6, MSX1, MAFB), increased lower facial heights (SNAI1), thinner and more retrusive lips and more protrusive foreheads (ABCA4-ARHGAP29, MAFB) in the nsCL/P relatives compared to controls. Disruption in early embryological development can lead to wide-ranging effects from subtle neurologic and facial features, which includes asymmetry, to significant impact on facial shape as characterized by a CL/P or in anomalies observed in craniofacial syndromes. Forensic Sci. doi: 10.1093/ije/dyr233, Richmond, S., Toma, A. M., and Zhurov, A. I. Couldn't necessarily say what exactly it is but yeah, but not Nat. No use, distribution or reproduction is permitted which does not comply with these terms. Am. Forensic Sci. Dentofacial Orthop. Similar levels of genetic-environmental contributions have been reported for some facial features. Forensic Sci. (2018). Top. Who is the most beautiful woman in Ireland? Forensic Sci. U.S.A. 114, 1016610171. Down syndrome, cleft lip and/or palate, Prader-Willi syndrome, and Treacher Collins syndrome can all present with facial abnormalities and genetic loci associated with them have been studied in relation to normal facial development (Boehringer et al., 2011; Brinkley et al., 2016). Cell Rep. 23, 15811597. (2017). 289, 4050. J. Med. Genet. doi: 10.1016/0002-9416(82)90073-2, Rivezzi, G., Piscitelli, P., Scortichini, G., Giovannini, A., Diletti, G., Migliorati, G., et al. A 3D morphometric perspective for facial gender analysis and classification using geodesic path curvature features. 15, 335346. Surg. Medical Image Understanding and Analysis. Genet. A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features. The disruption of neuro-facial developmental and maturational processes can lead to widespread and long-lasting abnormalities in central nervous system structure and functions and some of these disturbances will also be accompanied with subtle differences in facial features (Hennessy et al., 2010). Oral Pathol. (2009). A general model of dioxin contamination in breast milk: results from a study on 94 women from the Caserta and Naples areas in Italy. Curr. 45, 414419. 22, 12681271. Biol. There have been nine GWAS studies and it is appropriate to try and integrate their findings through a meta-analysis. Assessment and judgment of the face and body can be traced back to the ancient Greeks and Egyptians when mathematical methods such as Fibonacci series and the golden proportion (1:1.618) were applied to art and architecture as a method of defining attractiveness and beauty (Ricketts, 1982). doi: 10.1051/orthodfr/2009033. Further work is required to explore the importance of the various biomedical markers and medical conditions (e.g., fasting glucose, cholesterol, asthma, and neurological disorders etc.) Early growth genetics consortium. Although the molecular understanding of genetic variation influencing facial morphology is improving, the use of DNA as a prediction tool is still a long way off. A., Mattern, B. C., Claes, P., McEcoy, B., Hughes, C., and Shriver, M. D. (2017). WebDiscover the Northern Irish accent. Am. Hoyme, H. E., Kalberg, W. O., Elliott, A. J., Blankenship, J., Buckley, D., Marais, A. S., et al. Eur. Eur. 59(Suppl. Enhancers have a specific role in the expression of a target gene in different cells, anatomical regions and during different developmental time-points (Visel et al., 2009; Attanasio et al., 2013; Wilderman et al., 2018). Palate. J. Hum. Comput. A. The face develops very early in gestation and facial development is closely related to the cranial neural crest cells. WebScottish vs. Irish. They just released a fascinating study which aligns many pictures of individuals from every country and created composite images of what the average face would look like. The analytical techniques (particularly the bootstrapped response-based imputation modeling (BRIM) and hierarchical spectral clustering analysis) employed by Claes et al. Evolutionary psychology of facial attractiveness. bioRxiv. Subclinical features in non-syndromic cleft lip with or without cleft palate (CL/P): review of the evidence that subepithelial orbicularis oris muscle defects are part of an expanded phenotype for CL/P. Genet. 12:167. doi: 10.1038/nrg2933, Djordjevic, J., Jadallah, M., Zhurov, A. I., Toma, A. M., and Richmond, S. (2013a). Endogenous bone morphogenetic proteins regulate outgrowth and epithelial survival during avian lip fusion. doi: 10.1111/ocr.12012, Djordjevic, J., Lawlor, D. A., Zhurov, A. I., Toma, A. M., Playle, R., and Richmond, S. (2013b). Contrastingly, previous estimates suggest that antero-posterior face height, mandibular body length, ramus height, upper vermillion height, nasal width and maxillary protrusion are more strongly influenced by environmental factors (Jelenkovic et al., 2010; Djordjevic et al., 2016; Sidlauskas et al., 2016; Cole et al., 2017; Tsagkrasoulis et al., 2017). 15, 288298. Much confusion has arisen from the inaccurate use of the terms " Celt " and " Celtic." 32, 122. Dev. The US cancer moonshot initiative. Environ. Eur. Feeling a bit down, have a cup of tea. 1. Genet. Sci. Three-dimensional surface acquisition systems for the study of facial morphology and their application to maxillofacial surgery. Historically, craniofacial genetic research has understandably focused on identifying the causes of craniofacial anomalies and it has only been within the last 10 years, that there has been a drive to detail the biological basis of normal-range facial variation. Jaenisch, R., and Bird, A. Epigenetic processes include DNA methylation, histone modification and chromatin remodeling, which can affect gene expression by regulating transcription (Jaenisch and Bird, 2003; Bird, 2007; Gibney and Nolan, 2010; Allis and Jenuwein, 2016). Updated Clinical Guidelines for Diagnosing Fetal Alcohol Spectrum Disorders. Some reported genes appear to influence different parts of the face. 106, 191200. PLoS Genet. LH and SR wrote the section Estimating Identity. The pure Anglo Saxon type is Nordic looking like people from Scandinavia. The Celts originated in Asia minor and Iberia and would have absorbed man (2010). doi: 10.1002/rcs.141. Scottish is the term referred to peoples who live in Scotland, whereas Irish is the term that is referred to peoples who live in Ireland. Sharman, N. (2011). doi: 10.1038/s41588-018-0065-4, Farkas, L. G., Eiben, O. G., Sivkov, S., Tompson, B., Katic, M. J., and Forrest, C. R. (2004). WebYou may have porcelain, pale skin, or you may have freckles that outnumber the days of the year, but your features will be pleasantly proportioned and your eyes bright, with a genuine smile that lights up your face. However, large-scale population studies are needed to identify more genetic variants not only in the context of facial shape but general body development with particularly attention to puberty. 5, 213222. A 161a, 412. Epigenetics focuses on the functional components of the genes and gene activities. Orthod. Facial features can be broadly characterized in terms of the size and shape of the whole face and/or its component parts (e.g., big/small head; short/long and wide/thin face, prominent or retrusive chin). Admixture in Latin America: geographic structure, phenotypic diversity and self-perception of ancestry based on 7,342 individuals. Genomic medicine: health care issues and the unresolved ethical and social dilemmas. In the 2017 American Community Survey, 5.39 Reported shared influences of medical conditions, normal facial variation with associated genes. Standards from birth to maturity for height, weight, height velocity, and weight velocity: British children, 1965. Rep. 7:45885. doi: 10.1038/srep45885, Tzou, C. H., Artner, N. M., Pona, I., Hold, A., Placheta, E., Kropatsch, W. G., et al. doi: 10.1007/s00424-016-1807-8. doi: 10.1038/414909a, Leslie, E. J., Carlson, J. C., Shaffer, J. R., Butali, A., Bux, C. J., Castilla, E. E., et al. Those distillation processes might not seem like a big difference, but the effect is pretty pronounced. Maternal smoking during pregnancy is associated with mitochondrial DNA methylation. 10:e1004572. Exploratory genotype-phenotype correlations of facial form and asymmetry in unaffected relatives of children with non-syndromic cleft lip and/or palate. Genet. Biol. Mol. 6. Multiethnic GWAS reveals polygenic architecture of earlobe attachment. 8:e1002932. 50, 319321. 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