Young MA, Yanes T, Cust AE
… +9 more, Dunlop K, Limb S, Newson AJ, Purvis R, Thiyagarajan L, Scott RJ, Verma K, James PA, Steinberg J
Twin Res Hum Genet
· 2023 Feb · PMID 36950972
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Considerable progress continues to be made with regards to the value and use of disease associated polygenic scores (PGS). PGS aim to capture a person's genetic liability to a condition, disease, or a trait, combining in...Considerable progress continues to be made with regards to the value and use of disease associated polygenic scores (PGS). PGS aim to capture a person's genetic liability to a condition, disease, or a trait, combining information across many risk variants and incorporating their effect sizes. They are already available for clinicians and consumers to order in Australasia. However, debate is ongoing over the readiness of this information for integration into clinical practice and population health. This position statement provides the viewpoint of the Human Genetics Society of Australasia (HGSA) regarding the clinical application of disease-associated PGS in both individual patients and population health. The statement details how PGS are calculated, highlights their breadth of possible application, and examines their current challenges and limitations. We consider fundamental lessons from Mendelian genetics and their continuing relevance to PGS, while also acknowledging the distinct elements of PGS. Use of PGS in practice should be evidence based, and the evidence for the associated benefit, while rapidly emerging, remains limited. Given that clinicians and consumers can already order PGS, their current limitations and key issues warrant consideration. PGS can be developed for most complex conditions and traits and can be used across multiple clinical settings and for population health. The HGSA's view is that further evaluation, including regulatory, implementation and health system evaluation are required before PGS can be routinely implemented in the Australasian healthcare system.
Twin Res Hum Genet
· 2023 Feb · PMID 36943175
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A model in the form of a Markov chain is constructed to mimic variations in the human sex ratio. It is illustrated by simulation. The equilibrium distribution is shown to be a simple modification of the binomial distribu...A model in the form of a Markov chain is constructed to mimic variations in the human sex ratio. It is illustrated by simulation. The equilibrium distribution is shown to be a simple modification of the binomial distribution. This enables an easy calculation of the variation in sex ratio which could be expected in small populations.
Twin Res Hum Genet
· 2023 Feb · PMID 36924387
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The experience of going through the personal library of our late esteemed twin research colleague, Dr Irving I. Gottesman, is described. I came away with fond memories and unexpected treasures. This essay is followed by...The experience of going through the personal library of our late esteemed twin research colleague, Dr Irving I. Gottesman, is described. I came away with fond memories and unexpected treasures. This essay is followed by brief reviews of timely research on factors affecting callous-unemotional traits, depressive symptoms in prospective Chinese twin mothers, twins with sagittal suture craniosynostosis, and creative expressiveness and educational achievement. Media reports on informative topics of interest to researchers and the general public include male-female twin Holocaust survivors, nontuplets born in Mali, Indian twins who married the same man, twins born from the longest frozen embryos, an infant twin abduction and twins born in different years.
Arpawong TE, Gatz M, Zavala C
… +3 more, Gruenewald TL, Walters EE, Prescott CA
Twin Res Hum Genet
· 2023 Feb · PMID 36912114
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Estimated heritability of educational attainment (EA) varies widely, from 23% to 80%, with growing evidence suggesting the degree to which genetic variation contributes to individual differences in EA is highly dependent...Estimated heritability of educational attainment (EA) varies widely, from 23% to 80%, with growing evidence suggesting the degree to which genetic variation contributes to individual differences in EA is highly dependent upon situational factors. We aimed to decompose EA into influences attributable to genetic propensity and to environmental context and their interplay, while considering influences of rearing household economic status (HES) and sex. We use the Project Talent Twin and Sibling Study, drawn from the population-representative cohort of high school students assessed in 1960 and followed through 2014, to ages 68-72. Data from 3552 twins and siblings from 1741 families were analyzed using multilevel regression and multiple group structural equation models. Individuals from less-advantaged backgrounds had lower EA and less variation. Genetic variance accounted for 51% of the total variance, but within women and men, 40% and 58% of the total variance respectively. Men had stable genetic variance on EA across all HES strata, whereas high HES women showed the same level of genetic influence as men, and lower HES women had constrained genetic influence on EA. Unexpectedly, middle HES women showed the largest constraints in genetic influence on EA. Shared family environment appears to make an outsized contribution to greater variability for women in this middle stratum and whether they pursue more EA. Implications are that without considering early life opportunity, genetic studies on education may mischaracterize sex differences because education reflects different degrees of genetic and environmental influences for women and men.
Twin Res Hum Genet
· 2023 Feb · PMID 36896826
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Reading difficulties are prevalent worldwide, including in economically developed countries, and are associated with low academic achievement and unemployment. Longitudinal studies have identified several early childhood...Reading difficulties are prevalent worldwide, including in economically developed countries, and are associated with low academic achievement and unemployment. Longitudinal studies have identified several early childhood predictors of reading ability, but studies frequently lack genotype data that would enable testing of predictors with heritable influences. The National Child Development Study (NCDS) is a UK birth cohort study containing direct reading skill variables at every data collection wave from age 7 years through to adulthood with a subsample (final = 6431) for whom modern genotype data are available. It is one of the longest running UK cohort studies for which genotyped data are currently available and is a rich dataset with excellent potential for future phenotypic and gene-by-environment interaction studies in reading. Here, we carry out imputation of the genotype data to the Haplotype Reference Panel, an updated reference panel that offers greater imputation quality. Guiding phenotype choice, we report a principal components analysis of nine reading variables, yielding a composite measure of reading ability in the genotyped sample. We include recommendations for use of composite scores and the most reliable variables for use during childhood when conducting longitudinal, genetically sensitive analyses of reading ability.
Vanyukov MM, Maes HHM, Iacono WG
… +5 more, Kirisci L, Samek DR, Silberg JL, Zimmerman EB, Prom-Wormley EC
Twin Res Hum Genet
· 2023 Feb · PMID 36896815
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Illicit substance use is dangerous in both acute and chronic forms, frequently resulting in lethal poisoning, addiction, and other negative consequences. Similar to research in other psychiatric conditions, whose ultimat...Illicit substance use is dangerous in both acute and chronic forms, frequently resulting in lethal poisoning, addiction, and other negative consequences. Similar to research in other psychiatric conditions, whose ultimate goal is to enable effective prevention and treatment, studies in substance use are focused on factors elevating the risk for the disorder. The rapid growth of the substance use problem despite the effort invested in fighting it, however, suggests the need in changing the research approach. Instead of attempting to identify risk factors, whose neutralization is often infeasible if not impossible, it may be more promising to systematically reverse the perspective to the factors enhancing the aspect of liability to disorder that shares the same dimension but is opposite to risk, that is, resistance to substance use. Resistance factors, which enable the majority of the population to remain unaffected despite the ubiquity of psychoactive substances, may be more amenable to translation. While the resistance aspect of liability is symmetric to risk, the resistance approach requires substantial changes in sampling (high-resistance rather than high-risk) and using quantitative indices of liability. This article provides an overview and a practical approach to research in resistance to substance use/addiction, currently implemented in a NIH-funded project. The project benefits from unique opportunities afforded by the data originating from two longitudinal twin studies, the Virginia Twin Study of Adolescent and Behavioral Development and the Minnesota Twin Family Study. The methodology described is also applicable to other psychiatric disorders.
Li J, Kang X, Zhang T
… +5 more, Wang W, Xu C, Duan H, Tian X, Zhang D
Twin Res Hum Genet
· 2023 Feb · PMID 36852647
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An abnormal alanine aminotransferase (ALT) level is predictive of disease and all-cause mortality and may indicate liver injury. Using twin modeling, the genetic and environmental factors that affect human serum ALT leve...An abnormal alanine aminotransferase (ALT) level is predictive of disease and all-cause mortality and may indicate liver injury. Using twin modeling, the genetic and environmental factors that affect human serum ALT levels have been well studied for the populations in the different countries, and the results showed moderate-to-high heritability. However, the heritability of ALT level has not been explored in Chinese population. Thus, we recruited 369 pairs of twins (233 monozygotic and 136 dizygotic) from the Qingdao Twin Registry in China with a median age of 50 years (40-80 years). Correlation analysis and a structural equation model (SEM) were conducted to evaluate the heritability of ALT level. The data for age, gender, body mass index and alcohol consumption were set as covariates. Intrapair correlation in monozygotic twins was 0.64 (95%CI [.56, .71]) and 0.42 (95% CI [.28, .55]) in dizygotic twins. The SEM analysis indicated that 65% (95% CI [57%, 71%]) of the variation in ALT levels can be explained by additive genetics and 35% (95% CI [29%, 44%]) of the variation is attributed to unique environmental factors or residuals. Shared environmental influences were not significant. In conclusion, serum ALT variations exhibited strong genetic effects. The variation could also be explained by unique environmental factors. However, shared environmental factors have a minor impact on the serum ALT level.
Willoughby EA, Giannelis A, Iacono WG
… +2 more, McGue M, Vrieze SI
Twin Res Hum Genet
· 2022 Dec · PMID 36734056
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The University of Minnesota has played an important role in the resurgence and eventual mainstreaming of human behavioral genetics in psychology and psychiatry. We describe this history in the context of three major move...The University of Minnesota has played an important role in the resurgence and eventual mainstreaming of human behavioral genetics in psychology and psychiatry. We describe this history in the context of three major movements in behavioral genetics: (1) radical eugenics in the early 20th century, (2) resurgence of human behavioral genetics in the 1960s, largely using twin and adoption designs to obtain more precise estimates of genetic and environmental influences on individual differences in behavior; and (3) use of measured genotypes to understand behavior. University of Minnesota scientists made significant contributions especially in (2) and (3) in the domains of cognitive ability, drug abuse and mental health, and endophenotypes. These contributions are illustrated through a historical perspective of major figures and events in behavioral genetics.
Twin Res Hum Genet
· 2022 Dec · PMID 36633106
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Attention-deficit/hyperactivity disorder (ADHD) and obesity are positively associated, with increasing evidence that they share genetic risk factors. Our aim was to examine whether these findings apply to both types of A...Attention-deficit/hyperactivity disorder (ADHD) and obesity are positively associated, with increasing evidence that they share genetic risk factors. Our aim was to examine whether these findings apply to both types of ADHD symptoms for female and male adolescents. We used data from 791 girl and 735 boy twins ages 16-17 years to examine sex-specific phenotypic correlations between the presence of ADHD symptoms and overweight/obese status. For correlations exceeding .20, we then fit bivariate twin models to estimate the genetic and environmental correlations between the presence of ADHD symptoms and overweight/obese status. ADHD symptoms and height/weight were parent- and self-reported, respectively. Phenotypic correlations were .30 (girls) and .08 (boys) for inattention and overweight/obese status and .23 (girls) and .14 (boys) for hyperactivity/impulsivity and overweight/obese status. In girls, both types of ADHD symptoms and overweight/obese status were highly heritable, with unique environmental effects comprising the remaining variance. Furthermore, shared genetic effects explained most of the phenotypic correlations in girls. Results suggest that the positive association of both types of ADHD symptoms with obesity may be stronger in girls than boys. Further, in girls, these associations may stem primarily from shared genetic factors.
Twin Res Hum Genet
· 2022 Dec · PMID 36633100
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Quadruplets are at elevated physical risks at prenatal, perinatal, and postnatal levels, relative to twins. A brief review of this area is followed by discussion of a female quadruplet with three co-quadruplet brothers....Quadruplets are at elevated physical risks at prenatal, perinatal, and postnatal levels, relative to twins. A brief review of this area is followed by discussion of a female quadruplet with three co-quadruplet brothers. Next, several timely twin research reports are examined. The topics include antenatal corticosteroids and twins' neonatal outcomes, the meaning of fatherhood in families with twins, what doppelgängers (look-alikes) reveal about physical and behavioral similarity, and monozygotic (MZ) co-twin discordance for asymmetric pigmented paravenous chorioretinal atrophy. A lawsuit involving alleged cheating on a medical school examination by identical twins is also reviewed. General interest stories cover opposite-sex twin Holocaust survivors, twin models at a Gucci fashion show, twins with different fathers, reunited female twins who entered the same convent, the death of an MZ female twin soldier during training, and the surgical separation of conjoined twins in Brazil.
Ke J, Gao W, Wang B
… +13 more, Cao W, Lv J, Yu C, Huang T, Sun D, Liao C, Pang Y, Pang Z, Cong L, Wang H, Wu X, Liu Y, Li L
Twin Res Hum Genet
· 2022 Dec · PMID 36606461
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It is crucial to understand the genetic mechanisms and biological pathways underlying the relationship between obesity and serum lipid levels. Structural equation models (SEMs) were constructed to calculate heritability...It is crucial to understand the genetic mechanisms and biological pathways underlying the relationship between obesity and serum lipid levels. Structural equation models (SEMs) were constructed to calculate heritability for body mass index (BMI), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and the genetic connections between BMI and the four classes of lipids using 1197 pairs of twins from the Chinese National Twin Registry (CNTR). Bivariate genomewide association studies (GWAS) were performed to identify genetic variants associated with BMI and lipids using the records of 457 individuals, and the results were further validated in 289 individuals. The genetic background affecting BMI may differ by gender, and the heritability of males and females was 71% (95% CI [.66, .75]) and 39% (95% CI [.15, .71]) respectively. BMI was positively correlated with TC, TG and LDL-C in phenotypic and genetic correlation, while negatively correlated with HDL-C. There were gender differences in the correlation between BMI and lipids. Bivariate GWAS analysis and validation stage found 7 genes (, , , , , and ) that were possibly related to BMI and lipid levels. The significant biological pathways were the regulation of cholesterol reverse transport and the regulation of high-density lipoprotein particle clearance ( < .001). BMI and blood lipid levels were affected by genetic factors, and they were genetically correlated. There might be gender differences in their genetic correlation. Bivariate GWAS analysis found MIR144 gene and its related biological pathways may influence obesity and lipid levels.
Twin Res Hum Genet
· 2022 Dec · PMID 36606459
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The role of superficial anastomoses in the survival of fetuses with twin-twin transfusion syndrome after fetoscopic laser photocoagulation is unknown. This study aimed to evaluate how superficial anastomoses affect the c...The role of superficial anastomoses in the survival of fetuses with twin-twin transfusion syndrome after fetoscopic laser photocoagulation is unknown. This study aimed to evaluate how superficial anastomoses affect the circulatory dynamics of both fetuses with twin-twin transfusion syndrome using ductus venous Doppler waveforms. We included all twin-twin transfusion syndrome (TTTS) patients who underwent fetoscopic laser photocoagulation in our institution from 2006 to 2019; fetal demise cases after fetoscopic laser photocoagulation were excluded. We recorded ductus venous Doppler waveforms on the same day or one day before fetoscopic laser photocoagulation and one day after fetoscopic laser photocoagulation and measured the ductus venous pulsatility index and velocity ratios. We compared these -scores of donor and recipient twins between a group without superficial anastomoses and the groups with arterio-arterial or veno-venous anastomoses. A total of 115 surviving TTTS placentas after fetoscopic laser photocoagulation were analyzed. The ductus venous pulsatility index and all ratios were better in recipient twins with arterio-arterial anastomoses than in those without. The a-wave-related ratios were better in recipient twins with veno-venous anastomoses than in those without. Superficial anastomoses reduced the blood volume and arterio-arterial anastomoses protected the diastolic cardiac function in recipient twin-twin transfusion syndrome twins before fetoscopic laser photocoagulation. Superficial anastomoses in TTTS equilibrate blood pressure between donor and recipient twins.
Day K, McCubbin AJ, Murgia C
… +3 more, Southey MC, Brown J, Truby H
Twin Res Hum Genet
· 2022 Oct · PMID 36289562
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This case reports peripheral blood mononuclear cell (PBMC) transcriptomic changes in a pair of male monozygotic pediatric twins with metabolic syndrome (MetS) undertaking assisted weight loss. These 14-year-old boys pres...This case reports peripheral blood mononuclear cell (PBMC) transcriptomic changes in a pair of male monozygotic pediatric twins with metabolic syndrome (MetS) undertaking assisted weight loss. These 14-year-old boys presented with similar baseline biochemistry and body composition. After a 16-week weight-loss intervention, percent body weight loss was similar (Twin A 12%, and Twin B 13%). MetS resolved in Twin A but Twin B maintained elevated triglycerides after weight loss. Analysis of the PBMC transcriptome before and after weight loss revealed very different changes in gene expression including differences in the direction of expression of genes related to immune cell activation. 48.7% of genes that were downregulated in Twin A were upregulated in Twin B. This case highlights a novel approach to report the influence of chronic low-grade inflammation and metabolic dysfunction on the PBMC transcriptome. It explores whether expression of genes related to immune functions may underlie the differences in response to weight loss or whether transcriptomic alterations in immune cells may precede more traditional biomarkers of chronic pro-inflammation. These monozygotic twins present an example of divergence of phenotypic outcomes despite identical genetic background and similar treatment response.
Davis CN, Gizer IR, Colodro-Conde L
… +3 more, Statham DJ, Martin NG, Slutske WS
Twin Res Hum Genet
· 2022 Oct · PMID 36189823
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Genes associated with educational attainment may be related to or interact with adolescent alcohol, tobacco and cannabis use. Potential gene-environment interplay between educational attainment polygenic scores (EA-PGS)...Genes associated with educational attainment may be related to or interact with adolescent alcohol, tobacco and cannabis use. Potential gene-environment interplay between educational attainment polygenic scores (EA-PGS) and adolescent alcohol, tobacco, and cannabis use was evaluated with a series of regression models fitted to data from a sample of 1871 adult Australian twins. All models controlled for age, age, cohort, sex and genetic ancestry as fixed effects, and a genetic relatedness matrix was included as a random effect. Although there was no evidence that adolescent alcohol, tobacco or cannabis use interacted with EA-PGS to influence educational attainment, there was a significant, positive gene-environment correlation with adolescent alcohol use at all PGS thresholds (s <.02). Higher EA-PGS were associated with an increased likelihood of using alcohol as an adolescent (Δ ranged from 0.5% to 1.1%). The positive gene-environment correlation suggests a complex relationship between educational attainment and alcohol use that is due to common genetic factors.
Liu C, Su K, Liu G
… +5 more, Shang W, Wang X, Li C, Chen L, Zhou X
Twin Res Hum Genet
· 2022 Oct · PMID 36172934
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Whether assisted hatching (AH) is associated with a higher incidence of monozygotic twinning (MZT) in women undergoing assisted reproductive technology remains controversial; the aim of the study was to demonstrate the r...Whether assisted hatching (AH) is associated with a higher incidence of monozygotic twinning (MZT) in women undergoing assisted reproductive technology remains controversial; the aim of the study was to demonstrate the relationship between AH and MZT. A total of 8900 clinical pregnancies were selected among embryo transfer cycles from January 2011 to October 2019. Women receiving day (D) 3 embryos were divided into groups A-C: group A ( = 1651) and group B ( = 1045) included women aged ≤37 or ≥38 years, respectively, with zona pellucida (ZP) thinning; group C ( = 3865) included women aged ≤37 years without AH. Women aged ≤37 years who underwent blastocyst transfer and/or blastocyst ZP breaching were included in group D ( = 2339). The incidence of MZT was compared among groups A, B and C, and between groups C and D. The incidence of MZT in group B (2.2%) was significantly higher than in group A (1.0%), especially following intracytoplasmic sperm injection (ICSI), while the incidence of MZT in group A (1.0%) was significantly lower than in group C (2.2%). The MZT rate with in vitro fertilization was higher in group D (2.8%) than in group C (2.2%), but the MZT rate following ICSI was not significantly different between the two groups. ZP thinning of D3 embryos may increase the risk of MZT in older women (≥38 years), but decrease it in younger women (≤37 years). ZP breaching may be useful to reduce the incidence of MZT in ICSI-generated blastocysts.
Bode HF, Heikkinen A, Lundgren S
… +2 more, Kaprio J, Ollikainen M
Twin Res Hum Genet
· 2022 Oct · PMID 36073160
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DNA methylation-based age acceleration (DNAmAA) is associated with cancer, with both cancer tissue and blood showing increased DNAmAA. We aimed to investigate whether DNAmAA is associated with cancer risk within twin pai...DNA methylation-based age acceleration (DNAmAA) is associated with cancer, with both cancer tissue and blood showing increased DNAmAA. We aimed to investigate whether DNAmAA is associated with cancer risk within twin pairs discordant for cancer, and whether DNAmAA has the potential to serve as a biomarker for such. The study included 47 monozygotic and 48 same-sex-dizygotic cancer-discordant twin pairs from the Finnish Twin Cohort study with blood samples available between 17 and 31 years after the cancer diagnosis. We studied all cancers (95 pairs), then separately breast cancer (24 pairs) and all sites other than breast cancer (71 pairs). DNAmAA was calculated for seven models: Horvath, Horvath intrinsic epigenetic age acceleration, Hannum, Hannum intrinsic epigenetic age acceleration, Hannum extrinsic epigenetic age acceleration, PhenoAge and GrimAge. Within-pair differences in DNAmAA were analyzed by paired tests and linear regression. Twin pairs sampled before cancer diagnosis did not differ significantly in DNAmAA. However, the within-pair differences in DNAmAA before cancer diagnosis increased significantly the closer the cancer diagnosis was, and this acceleration extended for years after the diagnosis. Pairs sampled after the diagnosis differed for DNAmAA with the Horvath models capturing cancer diagnosis-associated DNAmAA across all three cancer groupings. The results suggest that DNAmAA in blood is associated with cancer diagnosis. This may be due to epigenetic alterations in relation to cancer, its treatment or associated lifestyle changes. Based on the current study, the biomarker potential of DNAmAA in blood appears to be limited.
Twin Res Hum Genet
· 2022 Oct · PMID 36053043
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Colorectal cancer is the third most common and second most deadly type of cancer worldwide, with approximately 1.9 million cases and 0.9 million deaths worldwide in 2020. Previous studies have shown that estrogen and tes...Colorectal cancer is the third most common and second most deadly type of cancer worldwide, with approximately 1.9 million cases and 0.9 million deaths worldwide in 2020. Previous studies have shown that estrogen and testosterone hormones are associated with colorectal cancer risk and mortality. However, the potential effect of their precursor, dehydroepiandrosterone sulfate (DHEAS), on colorectal cancer risk has not been investigated. Therefore, evaluating DHEAS's effect on colorectal cancer will expand our understanding of the hormonal contribution to colorectal cancer risk. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to investigate the causal effect of DHEAS on colorectal cancer. We obtained DHEAS and colorectal cancer genomewide association study (GWAS) summary statistics from the Leipzig Health Atlas and the GWAS catalog and conducted MR analyses using the TwoSampleMR R package. Our results suggest that higher DHEAS levels are causally associated with decreased colorectal cancer risk (odds ratio per unit increase in DHEAS levels score = 0.70; 95% confidence interval [0.51, 0.96]), which is in line with previous observations in a case-control study of colon cancer. The outcome of this study will be beneficial in developing plasma DHEAS-based biomarkers in colorectal cancer. Further studies should be conducted to interpret the DHEAS-colorectal cancer association among different ancestries and populations.
Bairnsfather JE, Ullén F, Osborne MS
… +2 more, Wilson SJ, Mosing MA
Twin Res Hum Genet
· 2022 Jun · PMID 35969033
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The relationship between pitch-naming ability and childhood onset of music training is well established and thought to reflect both genetic predisposition and music training during a critical period. However, the importa...The relationship between pitch-naming ability and childhood onset of music training is well established and thought to reflect both genetic predisposition and music training during a critical period. However, the importance of the amount of practice during this period has not been investigated. In a population sample of twins ( = 1447, 39% male, 367 complete twin pairs) and a sample of 290 professional musicians (51% male), we investigated the role of genes, age of onset of playing music and accumulated childhood practice on pitch-naming ability. A significant correlation between pitch-naming scores for monozygotic ( = .27, .001) but not dizygotic twin pairs ( = -.04, = .63) supported the role of genetic factors. In professional musicians, the amount of practice accumulated between ages 6 and 11 predicted pitch-naming accuracy ( = .025). In twins, age of onset was no longer a significant predictor once practice was considered. Combined, these findings are in line with the notion that pitch-naming ability is associated with both genetic factors and amount of early practice, rather than just age of onset per se. This may reflect a dose-response relation between practice and pitch-naming ability in genetically predisposed individuals. Alternatively, children who excel at pitch-naming may have an increased tendency to practice.