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Objective: This study investigated the role of nontypical development in the relative dominance in twins' relationships throughout childhood. Background: Dominance dynamics, affecting siblings' well‐being, are different in twins than in singletons for whom age and development often dictate sibling hierarchy. These dynamics in twins, who share similar ages and developmental contexts, remain underexplored and demand further understanding. Method: A longitudinal study surveyed 1,547 mothers and 536 fathers of 322 monozygotic (sharing nearly 100% genes) and 1,199 dizygotic (sharing 50% genetic variance) twin pairs, aged 3 to 8–9. Both parents reported on the twins' relationships. Mothers reported whether either twin had a developmental condition. Results: No dominance difference was found in similar developmental conditions dyads, whether both twins had typical or nontypical development. However, in dyads where twins differed in the developmental condition, nontypically developing twins were less dominant than their typically developing cotwins. This dominance imbalance persisted throughout childhood, even if initial developmental issues were resolved. Conclusion: From parents' perspectives, nontypical development does not, in itself, prevent children from demonstrating dominance behaviors in twinship, but it is more likely that the asymmetry in developmental conditions is associated with the relationship between the twins. Implications and Recommendations: According to parents' perceptions, twins with nontypical development might experience imbalances in their relationship throughout childhood when their co‐twin is a typically developing child. However, demonstrating dominance might be possible for them in other contexts. Understanding these dominance dynamics is vital for caregivers, informing tailored parenting strategies and interventions to support the well‐being of children. [ABSTRACT FROM AUTHOR]

Aim: Genetic influences on cerebral activity have been described previously, but data are scarce in preterms. We aimed to investigate whether a genetic influence causes amplitude-integrated electroencephalography (aEEG) signals to differ between singletons and twin preterm newborns. Methods: This was a retrospective single-centre study conducted at Innsbruck Medical University Hospital, Austria. Preterm infants born before 32 weeks of gestation between 6 November 2010 and 6 December 2022 were eligible for the study. The aEEG was analysed for the total maturation score, its component scores and the number of sleep--wake cycles per hour. Results: We enrolled 240 preterm twin infants (57.5% male) with a mean gestational age of 30 (range: 24-32) weeks and a mean birth weight of 1324 (range: 600--2116) grams. We compared 240 singleton matched preterms. No differences were found between preterm singletons and twin preterm infants regarding the total maturation and component scores, or the number of sleep--wake cycles. aEEG showed no difference between monozygotic and dizygotic twins. Conclusion: Compared to singletons, twin infants born preterm showed no differences in aEEG signals in the first 4 weeks of life. Future studies should include more complex non-invasive functional neuroimaging methods to gain more insight into this important topic. [ABSTRACT FROM AUTHOR]

This study examines the hypothesis that temperamental (dis)similarity is associated with twin relationship quality. In a longitudinal study that followed 322 monozygotic twins (who share close to 100% of their genes) and 1199 dizygotic twins (who on average, share 50% of their segregating genes) throughout childhood, mothers (N = 1547) and fathers (N = 536) reported on their twins' relationships on at least one of four measurement points when the twins were between 3 and 8–9 years of age. Mothers also reported on the twins' temperament. Negative associations were found between reports by both parents on the twins' closeness and their temperament difference throughout childhood, while positive associations were found between twins' conflict and their temperament difference in late childhood. Latent growth modeling indicated that the association between temperament differences and the twins' mother-reported closeness was evident beyond the effect of zygosity. A different pattern was found for twin conflict: the more the twins differed in their temperament (specifically negative emotionality) with age, the more the conflict between them increased. Our findings support the hypothesis that personality similarities can contribute to positive relationships from early childhood, and vice versa, beyond the effect of genetic similarity. [ABSTRACT FROM AUTHOR]

Spontaneous dizygotic (DZ) twins, i.e. twins conceived without the use of ARTs, run in families and their prevalence varies widely around the globe. In contrast, monozygotic (MZ) twins occur at a constant rate across time and geographical regions and, with some rare exceptions, do not cluster in families. The leading hypothesis for MZ twins, which arise when a zygote splits during preimplantation stages of development, is random occurrence. We have found the first series of genes underlying the liability of being the mother of DZ twins and have shown that being an MZ twin is strongly associated with a stable DNA methylation signature in child and adult somatic tissues. Because identical twins keep this molecular signature across the lifespan, this discovery opens up completely new possibilities for the retrospective diagnosis of whether a person is an MZ twin whose co-twin may have vanished in the early stages of pregnancy. Here, we summarize the gene finding results for mothers of DZ twins based on genetic association studies followed by meta-analysis, and further present the striking epigenetic results for MZ twins. [ABSTRACT FROM AUTHOR]

How the number of genome copies modifies the effect of random mutations remains poorly known. In yeast, researchers have investigated these effects for knock-out or other large-effect mutations, but have not accounted for differences at the mating-type locus. We set out to compare fitness differences among strains that differ in ploidy and/or zygosity using a panel of spontaneously arising mutations acquired in haploid yeast from a previous study. To ensure no genetic differences, even at the mating-type locus, we embarked on a series of transformations, which first sterilized and then temporarily introduced plasmid-borne mating types. Despite these attempts to equalize the haplotypes, fitness variation introduced during transformation swamped the differences among the original mutation-accumulation lines. While colony size looked normal, we observed a bi-modality in the maximum growth rate of our transformed yeast and determined that many of the slow growing lines were respiratory deficient ("petite"). Not previously reported, we found that yeast that were TID1/RDH54 knockouts were less likely to become petite. Even for lines with the same petite status, however, we found no correlation in fitness between the two replicate transformations performed. These results pose a challenge for any study using transformation to measure the fitness effect of genetic differences among strains. By attempting to hold haplotypes constant, we introduced more mutations that overwhelmed our ability to measure fitness differences between the genetic states. In this study, we transformed over one hundred different lines of yeast, using two independent transformations, and found that this common laboratory procedure can cause large changes to the microbe studied. Our study provides a cautionary tale of the need to use multiple transformants in fitness assays. [ABSTRACT FROM AUTHOR]

Identical twins challenge individual voice recognition applied in communication, criminal investigation, and health technologies. The similarities between siblings are due to the genetic heritage that produced either their vocal tract or the psychological processes acting since birth. To contribute to a precise individual identification by voice, we tested the hypothesis that even MZ siblings would differ in the spectral distribution of formants and sound quality. We recorded 86 same-sex twin pairs (71 MZ, 15 DZ 30 ± 12 years old) saying the Portuguese verse of “Hi, my name is (Pedro or Ana).” We trimmed the diphthong Ój (“Hi”) and measured f0, F1-F4 formants, jitter, shimmer, and Harmonic-to-noise ratio (HNR). As the male sampling was small, we compared only female twins using the Wilcoxon-matched test, the intrapair Correlation Coefficient (ICC), and GLMM models. On average, [Ój] lasted 0.24 ± 0.07 s, and f0 ranged from 469 to 510 kHz according to sex. We found no differences between the MZ or DZ sisters in any acoustic parameter, besides F1 for MZ ones. Also, MZ sisters were more alike (F1, jitter, HNR, weak; F3, F4 moderate) than DZ (only F1 high ICC). The interaction zygosity × age affected intrapair similarity, the older the sisters, the greater their differences. Short voice segments, like the diphthong [Ój], may not be good for differentiating identical twins but provide insights to discussion; F2, F4, and shimmer should be investigated in future studies considering males, younger participants, and other vocal expressions.

How the number of genome copies modifies the effect of random mutations remains poorly known. In yeast, researchers have investigated these effects for knock-out or other large-effect mutations, but have not accounted for differences at the mating-type locus. We set out to compare fitness differences among strains that differ in ploidy and/or zygosity using a panel of spontaneously arising mutations acquired in haploid yeast from a previous study. To ensure no genetic differences, even at the mating-type locus, we embarked on a series of transformations, which first sterilized and then temporarily introduced plasmid-borne mating types. Despite these attempts to equalize the haplotypes, fitness variation introduced during transformation swamped the differences among the original mutation-accumulation lines. While colony size looked normal, we observed a bi-modality in the maximum growth rate of our transformed yeast and determined that many of the slow growing lines were respiratory deficient (“petite”). Not previously reported, we found that yeast that were TID1/RDH54 knockouts were less likely to become petite. Even for lines with the same petite status, however, we found no correlation in fitness between the two replicate transformations performed. These results pose a challenge for any study using transformation to measure the fitness effect of genetic differences among strains. By attempting to hold haplotypes constant, we introduced more mutations that overwhelmed our ability to measure fitness differences between the genetic states. In this study, we transformed over one hundred different lines of yeast, using two independent transformations, and found that this common laboratory procedure can cause large changes to the microbe studied. Our study provides a cautionary tale of the need to use multiple transformants in fitness assays.

Wild grapevines are important genetic resources in breeding programs to confer adaptive fitness traits and unique fruit characteristics, but the genetics underlying these traits, and their evolutionary origins, are largely unknown. To determine the factors that contributed to grapevine genome diversification, we performed comprehensive intragenomic and intergenomic analyses with three cultivated European (including the PN40024 reference genome) and two wild North American grapevine genomes, including our newly released Vitis labrusca genome. We found the heterozygosity of the cultivated grapevine genomes was twice as high as the wild grapevine genomes studied. Approximately 30% of V. labrusca and 48% of V. vinifera Chardonnay genes were heterozygous or hemizygous and a considerable number of collinear genes between Chardonnay and V. labrusca had different gene zygosity. Our study revealed evidence that supports gene gain-loss events in parental genomes resulted in the inheritance of hemizygous genes in the Chardonnay genome. Thousands of segmental duplications supplied source material for genome-specific genes, further driving diversification of the genomes studied. We found an enrichment of recently duplicated, adaptive genes in similar functional pathways, but differential retention of environment-specific adaptive genes within each genome. For example, large expansions of NLR genes were discovered in the two wild grapevine genomes studied. Our findings support variation in transposable elements contributed to unique traits in grapevines. Our work revealed gene zygosity, segmental duplications, gene gain-and-loss variations, and transposable element polymorphisms can be key driving forces for grapevine genome diversification. [ABSTRACT FROM AUTHOR]

Background: Lipoprotein lipase (LPL) is the rate-limiting enzyme for triglyceride hydrolysis. Homozygous or compound heterozygous LPL variants cause autosomal recessive familial chylomicronemia syndrome (FCS), whereas simple heterozygous LPL variants are associated with hypertriglyceridemia (HTG) and HTG-related disorders. LPL frameshift coding sequence variants usually cause complete functional loss of the affected allele, thereby allowing exploration of the impact of different levels of LPL function in human disease. Methods: All exons and flanking intronic regions of LPL were Sanger sequenced in patients with HTG-related acute pancreatitis (HTG-AP) or HTG-AP in pregnancy. Previously reported LPL frameshift coding sequence variants were collated from the Human Gene Mutation Database and through PubMed keyword searching. Original reports were manually evaluated for the following information: zygosity status of the variant, plasma LPL activity of the variant carrier, disease referred for genetic analysis, patient's age at genetic analysis, and patient's disease history. SpliceAI was employed to predict the potential impact of collated variants on splicing. Results: Two novel rare variants were identified, and 53 known LPL frameshift coding sequence variants were collated. Of the 51 variants informative for zygosity, 30 were simple heterozygotes, 12 were homozygotes, and 9 were compound heterozygotes. Careful evaluation of the 55 variants with respect to their clinical and genetic data generated several interesting findings. First, we conclude that 6–7% residual LPL function could significantly delay the age of onset of FCS and reduce the prevalence of FCS-associated syndromes. Second, whereas a large majority of LPL frameshift coding sequence variants completely disrupt gene function through their "frameshift" nature, a small fraction of these variants may act wholly or partly as "in-frame" variants, leading to the generation of protein products with some residual LPL function. Third, we identified two candidate LPL frameshift coding sequence variants that may retain residual function based on genotype–phenotype correlation or SpliceAI-predicted data. Conclusions: This study reported two novel LPL variants and yielded new insights into the genotype–phenotype relationship as it pertains to LPL frameshift coding sequence variants. [ABSTRACT FROM AUTHOR]

Abstract Background National Persian school-aged twin registry was established to provide a platform for twin studies. In this report, we describe defining registry characteristics, database design, and preliminary results regarding gathered data in the first phase of the registry program. Method Through focus group discussions, the required data elements to design the database and data collection process were defined. First, a list of twins in school-aged groups was retrieved from the electronic database of the Ministry of Education. Tehran schools were selected for the first phase of our registry. Standard “Pea-in-Pods” questionnaire and twins’ similarity questionnaires were filled out by the parents themselves in addition to demographic information. Data were analyzed using SPSS v.22. Results The first national school-aged twin registry was established in 2018. Firstly, the required data sets and data collection process were defined using focus group discussions. At the country level, the initial information on 189,738 students was retrieved from the national database of the Ministry of Education. They were born between 2003 and 2017, of which 94,997 are boys (50.1%) and 94,741 are girls (49.9%). Of them, a total of 5,642 pairs of school-aged twins participated in the first phase of our program. Our sample size comprised 9772 twins, 906 triples, and 92 quadruplets. The analysis of the zygosity questionnaire showed that 14% of twin pairs were identified as monozygotic twins. Conclusion Recruiting school-aged twins through school health assistants leads to high enrollment and decreasing costs for the twin registry. The study showed a high rate of dizygotic twins that need to be verified by twin bio-sample in the next phase of studies.

We analyzed maternal plasma cell-free DNA samples from twin pregnancies in a prospective blinded study to validate a single-nucleotide polymorphism (SNP)-based non-invasive prenatal test (NIPT) for zygosity, fetal sex, and aneuploidy. Zygosity was evaluated by looking for either one or two fetal genome complements, fetal sex was evaluated by evaluating Y-chromosome loci, and aneuploidy was assessed through SNP ratios. Zygosity was correctly predicted in 100% of cases (93/93; 95% confidence interval (CI) 96.1%-100%). Individual fetal sex for both twins was also called with 100% accuracy (102/102; 95% weighted CI 95.2%-100%). All cases with copy number truth were also correctly identified. The dizygotic aneuploidy sensitivity was 100% (10/10; 95% CI 69.2%-100%), and overall specificity was 100% (96/96; 95% weighted CI, 94.8%-100%). The mean fetal fraction (FF) of monozygotic twins (n = 43) was 13.0% (standard deviation (SD), 4.5%); for dizygotic twins (n = 79), the mean lower FF was 6.5% (SD, 3.1%) and the mean higher FF was 8.1% (SD, 3.5%). We conclude SNP-based NIPT for zygosity is of value when chorionicity is uncertain or anomalies are identified. Zygosity, fetal sex, and aneuploidy are complementary evaluations that can be carried out on the same specimen as early as 9 weeks' gestation.

The aim of the study is to present two examples of twins with differences in their dentition revealed with the use of panoramic examinations. The analysis based on panoramic X-rays shows that even though the monozygotic twins share 100% of the genome, their dentitions reveal significant differences.

Villitis of unknown etiology (VUE), chronic chorioamnionitis (CC), chronic deciduitis (CD) and chronic histiocytic intervillositis (CHI) are most likely the result of a pathologic immune reaction caused by maternal anti-fetal rejection. We analyzed placentas of twin pregnancies with manifestation of these lesions in monozygotic and dizygotic instances. Twin pregnancies from our archive with at least one chronic inflammatory lesion were selected for further analysis and assessed concerning zygosity (gender, chorionicity, short tandem repeat (STR)-analysis). The cohort comprised sixteen twin placentas, monozygotic in five cases and dizygotic in 11 cases, respectively. VUE (n = 4), CC (n = 1) and CHI (n = 3) manifested concordantly in both placentas of the monozygotic pregnancies and affected discordantly one of the twin placentas in the dizygotic instances. CD (n = 10) manifested concordantly in two and discordantly in one of the monozygotic placentas, and concordantly in three and discordantly in four of the dizygotic instances. Intrauterine fetal demise (n = 3), preterm birth (n = 9) and low birth weight (n = 2) were recognized. Discordant fetal growth in live born children was recognized in two dizygotic cases with discordant manifestation of VUE and CHI. The concordant manifestation of VUE, CC and CHI in monozygotic and the discordant pattern of inflammation in dizygotic pregnancies points to pathologic immune mechanisms against genetically determined fetal antigens being essential for the development of these entities. The heterogenous manifestation of CD could be a hint for diverse fetal or maternal etiologic factors that may contribute to this lesion. • In monozygotic twin placentas most chronic inflammatory lesions manifest concordantly. • In dizygotic gestations these diseases mostly show a discordant manifestation pattern. • Discordant manifestation of the placental lesions may contribute to discordant growth of the babies. • Chronic deciduitis is the chronic inflammatoric entity that displays a heterogenous distribution pattern in twin placentas. [ABSTRACT FROM AUTHOR]

Our aim was to adapt and validate a Brazilian Portuguese version of the Twin Relationship Questionnaire developed by Fortuna et al. (2010) and validated by H. Segal and KnafoNoam (2019) in Israel. The respondents were 862 Brazilian mothers of twins (N = 1724 twins) with mean age of 35 years (SD = 6.1). The majority of the sample lived in the Southeast (61.8%) or in the South (24.5%) of Brazil. We conducted a Multilevel Confirmatory Factor Analysis with the pair of twins as second level variable, and the fivefactor structure (closeness, dependence, conflict, dominance, and rivalry) proposed by the original validation study of H. Segal and Knafo-Noam (2019) was confirmed. The final model retained 15 items out of 22 proposed in the original version of the questionnaire. Although the TRQ-BR has fewer items, the accuracy compared to the original questionnaire was maintained. Mixed Model Analysis (LMM) of TRQ scores were used to investigate twins’ relationships as a function of zygosity, age groups, and sex in order to provide evidence of convergent validity of the instrument. As expected, mothers perceived monozygotic twins (MZ) as more depedent than dizygotic twins (DZ). Furthermore, male twin pairs were considered more conflictive when compared to female twins. The present study showed that TRQ-BR is an adequate instrument for research purposes in the Brazilian population. It can also be useful for applied areas such as clinical and educational fields. [ABSTRACT FROM AUTHOR]

Background: National Persian school-aged twin registry was established to provide a platform for twin studies. In this report, we describe defining registry characteristics, database design, and preliminary results regarding gathered data in the first phase of the registry program. Method: Through focus group discussions, the required data elements to design the database and data collection process were defined. First, a list of twins in school-aged groups was retrieved from the electronic database of the Ministry of Education. Tehran schools were selected for the first phase of our registry. Standard “Pea-in-Pods” questionnaire and twins’ similarity questionnaires were filled out by the parents themselves in addition to demographic information. Data were analyzed using SPSS v.22. Results: The first national school-aged twin registry was established in 2018. Firstly, the required data sets and data collection process were defined using focus group discussions. At the country level, the initial information on 189,738 students was retrieved from the national database of the Ministry of Education. They were born between 2003 and 2017, of which 94,997 are boys (50.1%) and 94,741 are girls (49.9%). Of them, a total of 5,642 pairs of school-aged twins participated in the first phase of our program. Our sample size comprised 9772 twins, 906 triples, and 92 quadruplets. The analysis of the zygosity questionnaire showed that 14% of twin pairs were identified as monozygotic twins. Conclusion: Recruiting school-aged twins through school health assistants leads to high enrollment and decreasing costs for the twin registry. The study showed a high rate of dizygotic twins that need to be verified by twin bio-sample in the next phase of studies. [ABSTRACT FROM AUTHOR]

Background & aimsWe analyzed data from twins to determine how much the familial risk of colorectal cancer can be attributed to genetic factors vs environment. We also examined whether heritability is distinct for colon vs rectal cancer, given evidence of distinct etiologies.MethodsOur data set included 39,990 monozygotic and 61,443 same-sex dizygotic twins from the Nordic Twin Study of Cancer. We compared each cancer's risk in twins of affected co-twins relative to the cohort risk (familial risk ratio [FRR]). We then estimated the proportion of variation in risk that could be attributed to genetic factors (heritability).ResultsFrom earliest registration in 1943 through 2010, there were 1861 individuals diagnosed with colon cancer and 1268 diagnosed with rectal cancer. Monozygotic twins of affected co-twins had an FRR for colorectal cancer of 3.1 (95% confidence interval [CI], 2.4-3.8) relative to the cohort risk. Dizygotic twins of affected co-twins had an FRR for colorectal cancer of 2.2 (95% CI, 1.7-2.7). We estimated that 40% (95% CI, 33%-48%) of the variation in colorectal cancer risk could be attributed to genetic factors; unique environment only accounted for the remaining liability. For colon cancer, the FRR was 3.3 (95% CI, 2.1-4.5) for monozygotic twins and 2.6 (95% CI, 1.7-3.5) for dizygotic twins. For rectal cancer, comparable estimates were 3.3 (95% CI, 1.5-5.1) for monozygotic twins and 2.6 (95% CI, 1.2-4.0) for dizygotic twins. Heritability estimates for colon and rectal cancer were 16% (95% CI, 0-46%) and 15% (95% CI, 0-50%), common environment estimates were 15% (95% CI, 0-38%) and 11% (95% CI, 0-38%), and unique environment estimates were 68% (95% CI, 57%-79%) and 75% (95% CI, 61%-88%), respectively.ConclusionsInterindividual genetic differences could account for 40% of the variation in susceptibility to colorectal cancer; risk for colon and rectal cancers might have less of a genetic component than risk for colorectal cancer. Siblings, and particularly monozygotic co-twins, of individuals with colon or rectal cancer should consider personalized screening.

Gilles de la Tourette Syndrome (GTS) is a multifactorial neurodevelopmental disorder characterized by tics and multiple comorbidities. The pathophysiology is not yet fully understood, but both environmental and genetic risk factors seem to be involved. Twin studies provide important knowledge on genetic factors. We assessed the concordance of GTS and chronic tic disorders (CTD) in monozygotic (MZ) twins, and examined tic severity, symptoms of obsessive-compulsive disorder (OCD), attention deficit/hyperactivity disorder and autism spectrum disorder. Twin pairs, where at least one twin was diagnosed with any tic disorder, were identified through Danish Twin Registry, Psychiatric Central Registry, Danish National Patient Registry and National Tourette Clinic, Copenhagen University Hospital, Herlev. Zygosity was tested with single-nucleotide polymorphism (SNP) genotyping and clinical assessment was done with validated tools. 14 MZ twin pairs were included: five were discordant. Seven twin pairs were concordant for GTS, and for two pairs one twin had GTS and the other CTD. Among the twins with CTD or GTS, 50% had at least one comorbidity, which is higher than in background populations. The GTS + OCD-phenotype was significantly more frequent among GTS-concordant than among discordant twins. No statistically significant differences were found between the GTS-concordant and discordant twin pairs regarding tic severity or comorbidities. Thorough clinical assessment and SNP-based genotyping are important when conducting clinical twin studies. We found high concordance of GTS and CTD, which supports the notion that both disorders have common genetic risk factors. Further studies with larger cohorts including dizygotic twins are warranted for more conclusive results. • There is high concordance of tic disorders among monozygotic twins. • Gilles de la Tourette syndrome (GTS) and chronic tic disorders (CTD) are likely to have common genetic factors. • Nationwide registries are useful tools in epidemiological studies of GTS and CTD; however, the data should be validated clinically. • OCD occurs mainly among concordant, but not discordant GTS-twins supporting the notion of shared genetic factors underlying GTS and OCD. [ABSTRACT FROM AUTHOR]

Background: Patients with germline/somatic BRCA1/BRCA2 mutations (g/sBRCA1/2) comprise a distinct biologic subgroup of pancreas ductal adenocarcinoma (PDAC). Methods: Institutional databases were queried to identify patients who had PDAC with g/sBRCA1/2. Demographics, clinicopathologic details, genomic data (annotation sBRCA1/2 according to a precision oncology knowledge base for somatic mutations), zygosity, and outcomes were abstracted. Overall survival (OS) was estimated using the Kaplan‐Meier method. Results: In total, 136 patients with g/sBRCA1/2 were identified between January 2011 and June 2020. Germline BRCA1/2 (gBRCA1/2) mutation was identified in 116 patients (85%). Oncogenic somatic BRCA1/2 (sBRCA1/2) mutation was present in 20 patients (15%). Seventy‐seven patients had biallelic BRCA1/2 mutations (83%), and 16 (17%) had heterozygous mutations. Sixty‐five patients with stage IV disease received frontline platinum therapy, and 52 (80%) had a partial response. The median OS for entire cohort was 27.6 months (95% CI, 24.9‐34.5 months), and the median OS for patients who had stage IV disease was 23 months (95% CI, 19‐26 months). Seventy‐one patients received a poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor (PARPi), and 52 received PARPi monotherapy. For maintenance PARPi, 10 patients (36%) had a partial response, 12 (43%) had stable disease, and 6 (21%) had progression of disease as their best response. Six patients (21%) received maintenance PARPi for >2 years. For those with stage IV disease who received frontline platinum, the median OS was 26 months (95% CI, 20‐52 months) for biallelic patients (n = 39) and 8.66 months (95% CI, 6.2 months to not reached) for heterozygous patients (n = 4). The median OS for those who received PARPi therapy was 26.5 months (95% CI, 24‐53 months) for biallelic patients (n = 25) and 8.66 months (95% CI, 7.23 months to not reached) for heterozygous patients (n = 2). Conclusions: g/sBRCA1/2 mutations did not appear to have different actionable utility. Platinum and PARPi therapies offer therapeutic benefit, and very durable outcomes are observed in a subset of patients who have g/sBRCA1/2 mutations with biallelic status. In a cohort of 136 patients with pancreas cancer and a germline or somatic BRCA mutation, the median overall survival is 27.6 months (95% CI, 24.9‐34.5 months) for the entire cohort and 23 months for the stage IV cohort (n = 81). Biallelic zygosity enriches the response to platinum and poly(adenosine diphosphate ribose) polymerase inhibitor therapies. [ABSTRACT FROM AUTHOR]

Background: Diversity in the HLA genes might be associated with disease outcomes-the heterozygote advantage hypothesis. We tested this hypothesis in relation to hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).Methods: We utilized DNA from > 10 000 Taiwanese individuals with current or past HBV infection to examine the association between HLA diversity and critical natural history steps in the progression from HBV infection to HCC. Individuals were classified as homozygotes at a given locus when imputed to carry the same 4-digit allele for the 2 HLA alleles at that locus.Results: Increase in number of homozygous HLA class II loci was associated with an increased risk of chronic HBV infection (Ptrend = 1.18 × 10-7). Among chronic HBV carriers, increase in number of homozygous HLA class II loci was also associated with an increased risk of HBV-associated HCC (Ptrend = .031). For individual HLA loci, HLA-DQB1 homozygosity was significantly associated with HCC risk (adjusted hazard ratio = 1.40; 95% confidence interval, 1.06-1.84). We also found that zygosity affects risk of HCC through its ability to affect viral control.Conclusions: Homozygosity at HLA class II loci, particularly HLA-DQB1, is associated with a higher risk of HBV-associated HCC. [ABSTRACT FROM AUTHOR]

Assisted reproduction is presumed to increase monozygotic twin rates, with the possible contribution of laboratory and medical interventions. Monozygotic dichorionic gestations are supposed to originate from the splitting of an embryo during the first four days of development, before blastocyst formation. Single embryo transfers could result in dichorionic pregnancies, currently explained by embryo splitting as described in the worldwide used medical textbooks, or concomitant conception. However, such splitting has never been observed in human in vitro fertilization, and downregulated frozen cycles could also produce multiple gestations. Several models of the possible origins of dichorionicity have been suggested. However, some possible underlying mechanisms observed from assisted reproduction seem to have been overlooked. In this review, we aimed to document the current knowledge, criticize the accepted dogma, and propose new insights into the origin of zygosity and chorionicity. [ABSTRACT FROM AUTHOR]

Homozygosity at human leukocyte antigen (HLA) loci might lead to reduced immunosurveillance and increased disease risk, including cancers caused by infection or of hematopoietic origin. To investigate the association between HLA zygosity and risk of non-virus-associated solid tumors, we leveraged genome-wide association study (GWAS) data from over 28,000 individuals of European ancestry who participated in studies of 12 cancer sites (bladder, brain, breast, colon, endometrial, kidney, lung, ovary, pancreas, prostate, skin, and testis). Information on HLA zygosity was obtained by imputation; individuals were classified as homozygotes at a given locus when imputed to carry the same four-digit allele at that locus. We observed no evidence for an association between zygosity at six HLA loci and all cancers combined. Increase in number of homozygous at HLA class I loci, class II loci, or class I and II loci was also not associated with cancer overall (Ptrend = 0.28), with adjusted odds ratios (ORs) for risk-per-locus of 1.00 [95% confidence intervals (CIs) = 0.97, 1.03], 1.02 (0.99, 1.04), and 1.01 (0.99, 1.02), respectively. This study does not support a strong role for HLA zygosity on risk of non-virus-associated solid tumors.

Twin relationships have a significant effect on the twins' life and their families. In the first comprehensive study of this topic, our purpose was to examine the developmental courses of four dyadic dimensions of twins' relationships: closeness, dependence, conflict and rivalry, and the impact of zygosity and parenting on their relationships. Parents reported on their twins' relationships (N = 1547 mothers and 536 fathers with data from at least one of four measurement points from 3 to 8–9 years of age). The sample included 322 monozygotic twin dyads (sharing virtually 100% of their genes), and 1194 dizygotic twin dyads (sharing 50% of their genetic variance, on average). Our findings indicated that closeness and dependence decreased while rivalry increased through childhood. Dependence and rivalry also presented quadratic change. The twins' conflict increased only for dizygotic twins. As expected, we found that the twins' closeness and dependence were highly associated, as did the associations between conflict and rivalry. The mostly nonsignificant associations of closeness with conflict and rivalry reinforced the notion that they are not bi-polar opposites. However, dependence was positively related to the twins' conflict and rivalry. A zygosity effect was also evident as monozygotic twins had higher levels of closeness and dependence than dizygotic twins through childhood, but there was no significant difference in the levels of their conflict and rivalry. In congruence with family system theories, parental positivity predicted the twins' closeness and dependence, and parental negativity predicted the twins' dependence, conflict and rivalry. The results were discussed in light of an evolutionary perspective and the twins' developmental challenges through childhood. [ABSTRACT FROM AUTHOR]

Twins have an increased risk for congenital malformations and disruptions, including defects in brain morphogenesis. We analyzed data on brain imaging, zygosity, sex, and fetal demise in 56 proband twins and 7 less affected co‐twins with abnormal brain imaging and compared them to population‐based data and to a literature series. We separated our series into malformations of cortical development (MCD, N = 39), cerebellar malformations without MCD (N = 13), and brain disruptions (N = 11). The MCD group included 37/39 (95%) with polymicrogyria (PMG), 8/39 (21%) with pia‐ependymal clefts (schizencephaly), and 15/39 (38%) with periventricular nodular heterotopia (PNH) including 2 with PNH but not PMG. Cerebellar malformations were found in 19 individuals including 13 with a cerebellar malformation only and another 6 with cerebellar malformation and MCD. The pattern varied from diffuse cerebellar hypoplasia to classic Dandy–Walker malformation. Brain disruptions were seen in 11 individuals with hydranencephaly, porencephaly, or white matter loss without cysts. Our series included an expected statistically significant excess of monozygotic (MZ) twin pairs (22/41 MZ, 54%) compared to population data (482/1448 MZ, 33.3%; p =.0110), and an unexpected statistically significant excess of dizygotic (DZ) twins (19/41, 46%) compared to the literature cohort (1/46 DZ, 2%; p <.0001. Recurrent association with twin–twin transfusion syndrome, intrauterine growth retardation, and other prenatal factors support disruption of vascular perfusion as the most likely unifying cause. [ABSTRACT FROM AUTHOR]

Homozygosity at human leukocyte antigen (HLA) loci might lead to reduced immunosurveillance and increased disease risk, including cancers caused by infection or of hematopoietic origin. To investigate the association between HLA zygosity and risk of non-virus-associated solid tumors, we leveraged genome-wide association study (GWAS) data from over 28,000 individuals of European ancestry who participated in studies of 12 cancer sites (bladder, brain, breast, colon, endometrial, kidney, lung, ovary, pancreas, prostate, skin, and testis). Information on HLA zygosity was obtained by imputation; individuals were classified as homozygotes at a given locus when imputed to carry the same four-digit allele at that locus. We observed no evidence for an association between zygosity at six HLA loci and all cancers combined. Increase in number of homozygous at HLA class I loci, class II loci, or class I and II loci was also not associated with cancer overall (P trend = 0.28), with adjusted odds ratios (ORs) for risk-per-locus of 1.00 [95% confidence intervals (CIs) = 0.97, 1.03], 1.02 (0.99, 1.04), and 1.01 (0.99, 1.02), respectively. This study does not support a strong role for HLA zygosity on risk of non-virus-associated solid tumors. [ABSTRACT FROM AUTHOR]

Objective: To determine the ratio of dichorionic (DC) to monochorionic (MC) twins by maternal age.Methods: We reviewed all twin pregnancies undergoing first trimester screening (FTS) with nuchal translucency from April 2009 to December 2012 with sonographic determination of chorionicity. Cases were linked to newborn screening (NBS) results and zygosity estimated based on rates of fetal sex discordance. The ratio of DC to MC placentation by maternal age was calculated.Results: We identified 11,351 twin pregnancies with FTS and documented chorionicity. Among these, 7,861 (64.2%) had linked data on FTS and NBS to allow estimation of zygosity based on neonatal sex. Of these, 1,464 (18.6%) were MC and 6,406 (81.4%) DC. The MC twin rate remained constant while the DC twin rate increased with maternal age until 40y. At < 20y, 55% of twin pregnancies were monozygotic (MZ), as compared to 29% at ≥ 40y. Of MZ twins, 38% were DC at < 20y, while 53% were DC at ≥ 40y.Conclusions: Our data suggest a relationship of both zygosity and chorionicity with maternal age. DZ twinning increased with maternal age, while among MZ twins, the proportion that were DC also increased with maternal age. [ABSTRACT FROM AUTHOR]

The commentary delves into the implications of "assortative parenting" and "assortative cross-parenting," as introduced by N. L. Segal, and situates these concepts within the framework of current research. It addresses the joys and complexities of raising twins, highlighting how their concurrent development stages can amplify parental favoritism and heighten the challenge of addressing each twin's unique needs. This interplay provides a rich context to investigate assortative parenting practices. Additionally, this paper contemplates the broader picture of twin studies, particularly how the care of monozygotic twins (who share 100 % of their genes) and dizygotic twins (who share 50 % of their genes, on average) may reveal the intertwined nature of genetics and environment in parenting strategies. It also proposes that twins' interactions with other family members, their spouses, and peers can offer profound insights into the phenomena of phenotypic assortative affiliation, enriching our understanding of close relational bonds. • Discuss N. L. Segal's perspective on "assortative (cross) parenting." • Twin families provide for fruitful ground to understand close relationships. • Both genetic and environmental factors contribute to parenting styles. [ABSTRACT FROM AUTHOR]

Background: Conventional diagnosis of fragile X syndrome (FXS) is based on a combination of fragment analysis (FA) and Southern blotting (SB); however, this diagnostic approach is time- and labor-intensive and has pitfalls such as the possibility of missing large number alleles. Triplet repeat primed PCR (TP-PCR) is a current alternative used to overcome these limitations. We evaluated the diagnostic usefulness of TP-PCR compared with the conventional diagnostic protocol consisting of FA and/or SB in terms of allele categorization, repeat number correlation, and zygosity concordance in female genetic carriers. Methods: From November 2013 to March 2018, 458 patients (326 males, 132 females) were simultaneously examined using FA and/or SB and TP-PCR by detecting CGG repeat numbers in FMR1 gene and diagnosed as per American College of Medical Genetics guidelines. Results: The TP-PCR results showed high concordance with the FA and/or SB results for all three aspects (allele categorization, repeat number correlation, and zygosity concordance in female genetic carriers). TP-PCR detected CGG expansions =200 in all full mutation (FM) allele cases in male patients, as well as both the normal allele (NL) and FM allele in female carriers. In premutation (PM) allele carriers, the TP-PCR results were consistent with the FA and/or SB results. In terms of zygosity concordance in female genetic carriers, 12 NL cases detected by TP-PCR showed a merged peak consisting of two close heterozygous peaks; however, this issue was resolved using a 10-fold dilution. Conclusions: TP-PCR may serve as a reliable alternative method for FXS diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To examine the concordance rate of non‐chromosomal congenital malformations in twin pairs based on zygosity. Design: Retrospective cohort study. Setting: A tertiary hospital in Korea. Population: Twin pairs born at Seoul National University Hospital between 2001 and 2019. Methods: Congenital malformations were diagnosed by postnatal workups of neonates or autopsy in cases of stillborn infants. Zygosity was confirmed by sex, chorionicity and DNA analysis. Main outcome measures: Concordance rate of congenital malformations in twin pairs based on zygosity. Results: In total, 3386 twin pairs were included. The risk of a congenital malformation in the index twin increased significantly if the co‐twin had the congenital malformation, and the concordance rate was higher in monozygotic (MZ) than in dizygotic (DZ) twins (37.04 versus 16.77, P < 0.001). An increased risk of a congenital malformation in the presence of the same congenital malformation in the co‐twin was observed only for malformations of the nervous system, eye/ear/face/neck, circulatory system, cleft lip/palate, genital organs, urinary system and musculoskeletal system. Significantly higher concordance rates in MZ than in DZ twin pairs were observed only for the nervous system (40.00 versus 0.00, P < 0.001), circulatory system (32.97 versus 19.74, P = 0.021), cleft lip/palate (44.44 versus 0.00, P = 0.017) and urinary system (22.22 versus 0.00, P = 0.004), whereas significant differences were not found for the genital organs or musculoskeletal system. Conclusions: Monozygotic twins had higher concordance rates than DZ twins only in specific organ systems. It may be speculated that nervous system, circulatory system, cleft lip/palate and urinary system are primarily genetically affected. Monozygotic twins had higher concordance rates than dizygotic twins only in specific organ systems. Monozygotic twins had higher concordance rates than dizygotic twins only in specific organ systems. [ABSTRACT FROM AUTHOR]

We examined the item properties of the Two Peas Questionnaire (TPQ) among a sample of same-sex twin pairs from the Washington State Twin Registry. With the exception of the 'two peas' item, three of the mistakenness items showed differential item functioning. Results showed that the monozygotic (MZ) and dizygotic (DZ) pairs may differ in their responses on these items, even among those with similar latent traits of similarity and confusability. Upon comparing three classification methods to determine the zygosity of same-sex twins, the overall classification accuracy rate was over 90% using the unit-weighted pair zygosity sum score, providing an efficient and sufficiently accurate zygosity classification. Given the inherent nature of twin-pair similarity, the TPQ is more accurate in the identification of MZ than DZ pairs. We conclude that the TPQ is a generally accurate, but by no means infallible, method of determining zygosity in twins who have not been genotyped. [ABSTRACT FROM AUTHOR]

Zygosity refers to the degree of genetic similarity within each pair of twins. Monozygotic (identical) twins have the same genetic sequence, whereas dizygotic twins differ genetically as much as any pair of siblings. Accurate knowledge of zygosity is important for a range of reasons; yet incorrect information on whether twins are monozygotic or dizygotic is still given to twins and their parents. This article focuses on why zygosity testing is so important medically, socially, financially and ethically. [ABSTRACT FROM AUTHOR]

The study of twins provides a unique opportunity to evaluate the genetic and nongenetic contributions to a variance of multitude of traits. Twin research has revealed the impact of a strong genetic component to the variance of many dental traits. The present study was conducted to assess the dental caries and oral hygiene status in monozygotic (MZ) and dizygotic (DZ) twins. A random sample of 129 MZ and DZ twin pairs aged 6-15 years were included in this study. The zygosity of twin pairs was initially recorded by facial appearance and later determined by dermatoglyphics. Dental caries and oral hygiene status were recorded in these twin pairs and the data were subjected to statistical analysis. No significant difference was observed in the mean decayed, extracted due to caries and filled teeth (deft) in primary dentition and decayed, missing and filled (DMFT) in permanent dentition scores and oral hygiene status in MZ and DZ twin pairs. The similarity observed in oral health status reflects the effects of a shared environment in MZ and DZ twin pairs.

Twins Research Australia (TRA) is a community of twins and researchers working on health research to benefit everyone, including twins. TRA leads multidisciplinary research through the application of twin and family study designs, with the aim of sustaining long-term twin research that, both now and in the future, gives back to the community. This article summarizes TRA's recent achievements and future directions, including new methodologies addressing causation, linkage to health, economic and educational administrative datasets and to geospatial data to provide insight into health and disease. We also explain how TRA's knowledge translation and exchange activities are key to communicating the impact of twin studies to twins and the wider community. Building researcher capability, providing registry resources and partnering with all key stakeholders, particularly the participants, are important for how TRA is advancing twin research to improve health outcomes for society. TRA provides researchers with open access to its vibrant volunteer membership of twins, higher order multiples (multiples) and families who are willing to consider participation in research. Established four decades ago, this resource facilitates and supports research across multiple stages and a breadth of health domains. [ABSTRACT FROM AUTHOR]

The Netherlands Twin Register (NTR) is a national register in which twins, multiples and their parents, siblings, spouses and other family members participate. Here we describe the NTR resources that were created from more than 30 years of data collections; the development and maintenance of the newly developed database systems, and the possibilities these resources create for future research. Since the early 1980s, the NTR has enrolled around 120,000 twins and a roughly equal number of their relatives. The majority of twin families have participated in survey studies, and subsamples took part in biomaterial collection (e.g., DNA) and dedicated projects, for example, for neuropsychological, biomarker and behavioral traits. The recruitment into the NTR is all inclusive without any restrictions on enrollment. These resources - the longitudinal phenotyping, the extended pedigree structures and the multigeneration genotyping - allow for future twin-family research that will contribute to gene discovery, causality modeling, and studies of genetic and cultural inheritance. [ABSTRACT FROM AUTHOR]

This invited review aimed at presenting the evidence concerning neurodevelopmental outcomes, particularly cerebral palsy (CP), motor disability, cognitive impairment, mental retardation, any major disability, blindness and deafness in cases of twins, conceived after in vitro fertilization, presenting fetal/intrauterine growth restriction (FGR/IUGR) or being prematurely born. FGR/IUGR, prematurity and zygosity affect neurodevelopmental outcome; CP is higher in term infants, those presenting with FGR/IUGR, as well as in survivors of intrauterine co-twin death; cognitive ability of twins versus singletons mainly relates to confounding factors, as FGR/IUGR and prematurity, while evidence for differences in behavioral and psychiatric disorders between twins and singletons is limited. The impact of IVF per se has not been documented. Nevertheless, available literature, usually of heterogeneous and retrospective nature, diverges in the criteria for neurodevelopmental delay. Furthermore, differences in selection/exclusion criteria and small mixed cohorts, including the full range of complications, make comparison of the existing studies difficult. Future studies should focus in confirming the lack of IVF impact on twins' neurodevelopment and general health, in comparing long-term outcome of naturally conceived twins with those conceived following assisted reproduction techniques and in including evaluation of individual, longitudinal trajectories of growth, and development. In this respect, worldwide population-based registries will enable more precise description of neurodevelopmental outcomes among twins. [ABSTRACT FROM AUTHOR]

Introduction: A stronger correlation of physical traits among monozygotic (MZ) twins than dizygotic (DZ) twins indicates predominant contribution by genetic factors than environmental factors. Exploring the degree of resemblance in tooth morphometry and the pattern of rugae among twins shall aid in forensic identification. Aim and Objective: To find out the degree of correlation in tooth morphometry and the palatal rugae pattern among MZ and DZ twins. Materials and Methods: The maximum coronal mesiodistal and buccolingual dimensions of the maxillary teeth excluding the second and third molars in 21 pairs of MZ and 12 pairs of DZ twins along with a MZ triplet were recorded using digital calipers calibrated to 0.01 mm. The dimensions of the teeth based on the number, shape, size, and the unification palatal rugae pattern among twin pairs were analyzed and recorded. Results: Our results suggest a stronger correlation of tooth dimension among MZ than DZ twins, which differs for individual maxillary tooth. There may be a separate set of genes responsible for controlling the mesiodistal and buccolingual tooth dimensions. The maxillary canine and maxillary premolars do show the least amount of genetic variability. The results in our study provide remarkable evidence regarding the existence of mirror imaging in tooth dimension as well as the number and shape of the palatal rugae. Conclusion: This first of its kind study in the Indian population suggests a remarkable similarity with regard to the tooth’s size and uniqueness of the palatal rugae pattern among MZ and DZ twins, which suggests their strong inheritability potential. This may be useful as additional tools for zygosity determination along with other dental traits. The significant evidence of mirror imaging of tooth dimension and rugae shall definitely contribute to the concept of development of human body.

Spontaneous dizygotic (DZ) twins, i.e. twins conceived without the use of ARTs, run in families and their prevalence varies widely around the globe. In contrast, monozygotic (MZ) twins occur at a constant rate across time and geographical regions and, with some rare exceptions, do not cluster in families. The leading hypothesis for MZ twins, which arise when a zygote splits during preimplantation stages of development, is random occurrence. We have found the first series of genes underlying the liability of being the mother of DZ twins and have shown that being an MZ twin is strongly associated with a stable DNA methylation signature in child and adult somatic tissues. Because identical twins keep this molecular signature across the lifespan, this discovery opens up completely new possibilities for the retrospective diagnosis of whether a person is an MZ twin whose co-twin may have vanished in the early stages of pregnancy. Here, we summarize the gene finding results for mothers of DZ twins based on genetic association studies followed by meta-analysis, and further present the striking epigenetic results for MZ twins., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Twin bonds, likely the most enduring of human relationships, provide both solace and rivalry for twins. Using an evolutionary psychology perspective, this chapter scrutinizes twins' bonds from prenatal stages to childhood to better understand their unique relationships. Twins' interactions, which begin in the womb, establish patterns of cooperation and competition. The initial years pose parenting challenges that shape the twins' experiences of dependency and rivalry. As twins grow, five dimensions-closeness, dependence, conflict, rivalry, and dominance-emerge, evolving distinctly between monozygotic twins (MZ: sharing close to 100% of their genes) and dizygotic twins (DZ: sharing on average 50% of their genetic variance). The chapter notes the closer relationship MZ twins share compared to DZ twins. While the closeness and dependence among DZ twins decline throughout childhood, these elements remain stable in MZ twins. The effect of zygosity on conflict and rivalry is less clear. For both MZ and DZ twins, conflict stays steady, while rivalry intensifies with school entry, probably driven by external comparisons, but lessens as twins develop into late childhood. Unlike singletons, where birth order dictates dominance dynamics, in twins, this dynamic is more variable and becomes more defined by around 6.5 years of age. Several factors are presented as impacting the nature of the twins' relationships: the evolvement of 'twin language', the parenting style and the differential parenting they receive. This exploration into the development of twins' relationships underlines the importance of tailored caregiving and invites further research into the genetic and environmental factors that shape close bonds., (Copyright © 2024. Published by Elsevier Inc.)

The giant panda, native to mountains of south-west China, is one of the world's rarest bear species and is subject to considerable conservation effort. In captivity, the proportion of twins accounts for 54% of the total number of births. To date, little is known about zygosity in panda populations - specifically, the proportion of monozygotic and dizygotic twins. In this study, we used 10 microsatellite markers for reliable zygosity testing, and the probability of monozygotic twins was 99.963% when all 10 markers were concordant. Out of 43 studied twin pairs, no MZ twins were found, indicating that there may be no identical panda twins (or the incidence is very low). We speculate that the fertilized eggs of giant pandas do not have the capability to split into two identical embryos, or that this ability is very poor, which is likely due to delayed implantation that is common in bear species. The results of this study deepen our understanding of giant panda breeding, yield insight into panda twins' likely mechanism of formation, and reduce the uncertainty of individual identity in wild population surveys. [ABSTRACT FROM AUTHOR]

Objective: To assess the clinical characteristics of fetal aneuploidy between dichorionic twins (DCT) and monochorionic twins (MCT) undergoing invasive prenatal diagnosis.Methods: Twin fetuses undergoing invasive prenatal diagnosis were enrolled in this study. All twin fetuses were classified into 2 groups according to chorionicity. The rates of fetal aneuploidy in different groups were compared.Result: This study included 1,714 fetuses (857 sets of twin pairs); among them, 1,190 were DCT and 524 were MCT. Overall, the rate of aneuploidy was 4.7% (56/1,190) in DCT and 3.4% (18/524) in MCT. Sixty-four (86.5%, 64/74) fetal aneuploidies occurred in only one fetus of the twin pairs. In DCT, the most common aneuploidy was trisomy 21 (53.6%, 30/56), followed by trisomy 18 (21.4%, 12/56) and trisomy 13 (8.9%, 5/56), while in MCT, the most common aneuploidy was Turner syndrome (33.3%, 6/18), followed by trisomy 21 (27.7%, 5/18) and 47,XYY (11.0%, 2/18).Conclusion: Aneuploidy mostly occurred in only one fetus in the twin pairs. The most common aneuploidy was trisomy 21 in DCT and Turner syndrome in MCT. Dual amniocentesis should be performed when discordant monozygotic twins are suspected. [ABSTRACT FROM AUTHOR]

Background: Individuals with impaired fat taste (FT) sensitivity have reduced satiety responses after consuming fatty foods, leading to increased dietary fat intake. Habitual consumption of dietary fat may modulate sensitivity to FT, with high consumption decreasing sensitivity [increasing fatty acid taste threshold (FATT)] and low consumption increasing sensitivity (decreasing FATT). However, some individuals may be less susceptible to diet-mediated changes in FATT due to variations in gene expression. Objective: The objective of this study was to determine the effect of an 8-wk low-fat or high-fat diet on FATT while maintaining baseline weight (<2.0 kg variation) to assess heritability and to explore the effect of genetics on diet-mediated changes in FATT. Design: A co-twin randomized controlled trial including 44 pairs (mean ± SD age: 43.7 ± 15.4 y; 34 monozygotic, 10 dizygotic; 33 women, 10 men, 1 gender-discordant) was conducted. Twins within a pair were randomly allocated to an 8-wk low-fat (<20% of energy from fat) or high-fat (>35% of energy from fat) diet. FATT was assessed by a 3-alternate forced choice methodology and transformed to an ordinal scale (FT rank) at baseline and at 4 and 8 wk. Linear mixed models were fit to assess diet effect on FT rank and diet effect modification due to zygosity. A variance components model was fit to calculate baseline heritability. Results: There was a significant time x diet interaction for FT rank after the 8-wk trial (P < 0.001), with the same conclusions for the subset of participants maintaining baseline weight (low-fat; n = 32; high-fat: n = 35). There was no evidence of zygosity effect modification (interaction of time x diet x zygosity: P = 0.892). Heritability of baseline FT rank was 8%. Conclusions: There appears to be little to no genetic contribution on heritability of FATT or diet-mediated changes to FATT. Rather, environment, specifically dietary fat intake, is the main influencer of FT sensitivity, regardless of body weight. [ABSTRACT FROM AUTHOR]