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Research Publications

The following is a list of Avera’s research publications in addition to collaborative manuscripts between Avera Institute for Human Genetics researchers and other national and international institutions.

Avera Institute for Human Genetics Publications

Candidate gene associations with withdrawn behavior

The Journal of Child Psychology and Psychiatry, 2013

BACKGROUND: Social withdrawal is a core neuropsychiatric phenomenon in developmental psychopathology. Its presence predicts psychopathology across many domains, including depression, psychosis, autism, anxiety, and suicide. Withdrawn behavior is highly heritable, persistent, and characteristically worsens without intervention. To date, few studies have successfully identified genetic associations with withdrawn behavior, despite the abundance of evidence of its heritability. This may be due to reliance of categorical over dimensional measures of the behaviorally inhibited phenotype. The aim of this study is to identify associations between known psychiatric candidate genes and a dimensionally derived measure of withdrawn behavior.

METHODS: Genetic information was collected on 20 single-nucleotide polymorphisms (SNPs) from a custom-designed SNP chip and TAQMAN arrays of 4 variable number of tandem repeat (VNTR) genes for 551 individuals from 187 families. Linear mixed modeling was employed to examine the relationship between genotypes of interest and Child Behavior Checklist (CBCL) Withdrawn Behavior Subscale Score (WBS) while controlling for gender and age through multiple linear regressions.

RESULTS: Withdrawn behavior was highly associated with polymorphism rs6314 of the serotonin receptor 2A (HTR2A) [p = 0.009, estimate = 0.310 (bootstrap 95% CI 0.155-0.448), bootstrap p=0.001] and rs1800544 of the alpha 2-adrenergic (ADRA2A) [p = .001, estimate = -0.310 (bootstrap 95% CI -0.479 to -0.126), bootstrap p = .001] genes after correction for gender and age. The association between withdrawn behavior and ADRA2A was stronger for younger children.

CONCLUSIONS: HTR2A and ADRA2A genes are associated with withdrawn behavior. This reinforces the role of catecholaminergic genes in the heritability of withdrawn behavior.

A prospective study of the effects of breastfeeding and FADS2 polymorphisms on cognition and hyperactivity/attention problems

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2013

Abstract: Breastfeeding has been associated with improved cognitive functioning. There is a beneficial effect on IQ, and possibly on associated phenotypes such as attention problems. It has been suggested that the effect on IQ is moderated by polymorphisms in the FADS2 gene, which is involved in fatty acid metabolism. In this study we tested the relation between breastfeeding and FADS2 polymorphisms on the one hand and IQ, educational attainment, overactivity, and attention problems on the other hand. IQ at age 5, 7, 10, 12, and/or 18 (n = 1,313), educational attainment at age 12 (n = 1,857), overactive behavior at age 3 (n = 2,560), and attention problems assessed at age 7, 10, and 12 years (n = 2,479, n = 2,423, n = 2,226) were predicted by breastfeeding and two SNPs in FADS2 (rs174575 and rs1535). Analyses were performed using structural equation modeling. After correction for maternal education, a main effect of breastfeeding was found for educational attainment at age 12 and overactive behavior at age 3. For IQ, the effect of breastfeeding across age was marginally significant (P = 0.05) and amounted to 1.6 points after correcting for maternal education. Neither a main effect of the FADS2 polymorphisms nor an interaction with breastfeeding was detected for any of the phenotypes. This developmentally informed study confirms that breastfeeding is associated with higher educational attainment at age 12, less overactive behavior at age 3 and a trend toward higher IQ after correction for maternal education. In general, the benefits of breastfeeding were small and did not interact with SNPs in FADS2.

Population structure, migration, and diversifying selection in the Netherlands

European Journal of Human Genetics, 2013

Abstract: Genetic variation in a population can be summarized through principal component analysis (PCA) on genome-wide data. PCs derived from such analyses are valuable for genetic association studies, where they can correct for population stratification. We investigated how to capture the genetic population structure in a well-characterized sample from the Netherlands and in a worldwide data set and examined whether (1) removing long-range linkage disequilibrium (LD) regions and LD-based SNP pruning significantly improves correlations between PCs and geography and (2) whether genetic differentiation may have been influenced by migration and/or selection. In the Netherlands, three PCs showed significant correlations with geography, distinguishing between: (1) North and South; (2) East and West; and (3) the middle-band and the rest of the country. The third PC only emerged with minimized LD, which also significantly increased correlations with geography for the other two PCs. In addition to geography, the Dutch North-South PC showed correlations with genome-wide homozygosity (r=0.245), which may reflect a serial-founder effect due to northwards migration, and also with height (♂: r=0.142, ♀: r=0.153). The divergence between subpopulations identified by PCs is partly driven by selection pressures. The first three PCs showed significant signals for diversifying selection (545 SNPs - the majority within 184 genes). The strongest signal was observed between North and South for the functional SNP in HERC2 that determines human blue/brown eye color. Thus, this study demonstrates how to increase ancestry signals in a relatively homogeneous population and how those signals can reveal evolutionary history.

Lipid-lowering effect of berberine in human subjects and rats

Phytomedicine, 2012

Abstract: Due to serious adverse events and the limited effectiveness of currently available pharmacological therapies for obesity, many research efforts have focused on the development of drugs from natural products. Our previous studies demonstrated that berberine, an alkaloid originally isolated from traditional Chinese herbs, prevented fat accumulation in vitro and in vivo. In this pilot study, obese human subjects (Caucasian) were given 500 mg berberine orally three times a day for twelve weeks. The efficacy and safety of berberine treatment was determined by measurements of body weight, comprehensive metabolic panel, blood lipid and hormone levels, expression levels of inflammatory factors, complete blood count, and electrocardiograph. A Sprague-Dawley rat experiment was also performed to identify the anti-obesity effects of berberine treatment. The results demonstrate that berberine treatment produced a mild weight loss (average 5 lb/subject) in obese human subjects. But more interestingly, the treatment significantly reduced blood lipid levels (23% decrease of triglyceride and 12.2% decrease of cholesterol levels) in human subjects. The lipid-lowering effect of berberine has also been replicated in the rat experiment (34.7% decrease of triglyceride and 9% decrease of cholesterol levels). Cortisol, calcitriol, ACTH, TSH, FT4, and SHBG levels were not significantly changed following 12 weeks of berberine treatment. However, there was interestingly, an increase in calcitriol levels seen in all human subjects following berberine treatment (mean 59.5% increase, p=0.11). Blood inflammatory factors (CRP, IL-6, TNFα, COX-2) and erythrocyte sedimentation rate (ESR) were not significantly affected by treatment with berberine. Tests of hematological, cardiovascular, liver, and kidney function following berberine treatment showed no detrimental side effects to this natural compound. Collectively, this study demonstrates that berberine is a potent lipid-lowering compound with a moderate weight loss effect, and may have a possible potential role in osteoporosis treatment/prevention.

De novo and inherited CNVs in MZ twin pairs selected for discordance and concordance on Attention Problems

European Journal of Human Genetics, 2012

Abstract: Copy number variations (CNVs) have been reported to be causal suspects in a variety of psychopathologic traits. We investigate whether de novo and/or inherited CNVs contribute to the risk for Attention Problems (APs) in children. Based on longitudinal phenotyping, 50 concordant and discordant monozygotic (MZ) twin pairs were selected from a sample of ~3200 MZ pairs. Two types of de novo CNVs were investigated: (1) CNVs shared by both MZ twins, but not inherited (pre-twinning de novo CNVs), which were detected by comparing copy number (CN) calls between parents and twins and (2) CNVs not shared by co-twins (post-twinning de novo CNVs), which were investigated by comparing the CN calls within MZ pairs. The association between the overall CNV burden and AP was also investigated for CNVs genome-wide, CNVs within genes and CNVs outside of genes. Two de novo CNVs were identified and validated using quantitative PCR: a pre-twinning de novo duplication in a concordant-unaffected twin pair and a post-twinning deletion in the higher scoring twin from a concordant-affected pair. For the overall CNV burden analyses, affected individuals had significantly larger CNVs may increase the risk for AP, because they are more likely to affect genes, and confirms that MZ twins are not always genetically identical.

COMT Val158Met Genotype as a Risk Factor for Problem Behaviors in Youth

Journal of the American Academy of Child & Adolescent Psychiatry, 2010

Objective: To test the association between the catechol-O-methyltransferase (COMT) Val158Met polymorphism and both aggressive behavior and attention problems in youth. We hypothesized that youth carrying a Met allele would have greater average aggressive behavior scores, and that youth exhibiting Val-homozygosity would have greater average attention problems scores.

Method: Complete data on maternally rated Child Behavior Checklist (CBCL) measures of aggressive behavior (AGG) and attention problems (AP), COMT polymorphism data, demographics, and maternal parenting quality were available for 149 youth (6 to 18 years old). Multivariable linear regression models were used to test the degree to which youth COMT Val158Met genotype was associated with AGG and AP while statistically controlling for age, gender, parental socioeconomic status (SES), and maternal parenting quality from the Alabama Parenting Questionnaire.

Results: Mothers of Met-carriers rated their children higher on average AGG scores when compared with mothers of Val-homozygotes (p=0.016). Further analyses revealed that this association was even more robust for maternal ratings of direct aggression (p=0.007). The hypothesized association between Val-homozygosity and higher average AP scores relative to average AP scores of Met-carriers did not quite reach statistical significance (p=0.062).

Conclusions: After controlling for demographics, SES, and maternal parenting quality as cofounders, there remains a strong association between youth carrying a Met allel and higher average AGG scores relative to Val-homozygotes.

Berbine Inhibits SREBP-1-related Clozapine and Risperidone Induced Adipogenesis in 3T3-L1 Cells

Phytotherapy Research, 2010

Weight gain is a common and potentially serious complication associated with the treatment of second generation antipsychotics such as clozapine and risperidone. Increased peripheral adipogenesis via the SREBP-1 pathway could be one critical mechanism responsible for antipsychotic drug-induced weight gain. Berberine, a botanic alkaloid, has been shown in our previous studies to inhibit adipogenesis in cell and animal models. MTT was used to determine the sytotoxic effects of clozapine and risperidone in combination with berberine. Differentiation of 3T3-L1 cells was monitored by Oil-Red-O staining and the expression of SREBP-1 and related proteins was determined by real-time RT-PCR and western blotting. The results showed that neither clozapine nor risperidone, alone or in combination with berberine, had significant effects on cell viability. Eight days treatment with 15 µM clozapine increased adipogenesis by 37.4% and 50 µM risperidone increased adipogenesis by 26.5% during 3T3-L1 cell differentiation accompanied by increased SREBP-1, PPAR?, C/EBPa, LDLR and Adiponectin gene expression. More importantly, the addition of 8 uM berberine diminshed the uinduction of adipogenesis almost completely accompanied by down-regulated mRNA and protein expression levels of SREBP-1-related proteins. These encouraging results may lead to the use of berberine as an adjuvant to prevent weight gain during second generation antipsychotic medication.

Inhibitory effect and transcriptional impact of berberine and evodiamine on human white preadipocyte differentiation

Fitoterapia, 2009

Abstract: It has been reported that the botanical alkaloids, berberine and evodiamine, inhibit mouse preadipocyte 3T3-L1 differentiation. The aim of this study was to investigate the effect and transcriptional impact of berberine and evodiamine individually and in combination on human white preadipocyte (HWP) differentiation. We have shown that the treatment with 8 µM berberine of 4 µM evodiamine resulted in a major inhibition of HWP differentiation accompanied by up-regulation of both GATA binding protein 2 and 3 (GATA-2 and GATA-3) mRNA and protein expression, suggesting that both compounds may have excellent potential as agents to prevent obesity.

Effects of glutathione reuctase inhibition on cellular thiol redox state and related systems

Archives of Biochemistry and Biophysics, 2009

Abstract: Although inhibition of glutatione reductase (GR) has been demonstrated to cause a decrease in reduced glutathione (GSH) and increase in glutathione disulfide (GSSG), a systematic study of the effects of GR inhibition on thio redox state and related systems has not been noted. By employing a monkey kidney cell line as the cell model and 2-acetylamino-3-[4-(2-acetylamino-2-carboxy-ethylsulfanylthio carbonylamino)phenylthiocarbamoylsulfanyl]propionic acid (2-AAPA) as a GR inhibitor, an investigation of the effects of GR inhibition on cellular thio redox state and related systems was conducted. Our study demonstrated that, in addition to a decrease in GSH and increase in GSSG, 2-AAPA increased the ratios of NADH/NAD+ and NADHP/NADP+. Significant protein glutationylation was observed. However, the inhibition did not effect the formation of reactive oxygen species or expression of antioxidant defense enzyme systems [GR, glutathione peroxidase, catalase, and superoxide dismutase] and enzymes involved in GSH biosynthesis [?-glutamylcysteine synthetase and glutathione synthetase].

Berberine inhibits adipogensis in high-fat diet-induced obesity mice

Fitoterapia, 2009

Abstract: Our previous studies illustrated that berberine inhibited adipogenesis in murine-derived 3T3-L1 preadipocytes and human white adipocytes. In this study, the effects of berberine on the adipogensis of high-fat diet-induced obesity (FD) or normal diet (ND) mice and possible transcriptional impact are investigated. The results demonstrated that in FD mice, berberine reduced mouse weight gain and food intake and serum glucose, triglyceride, and total cholesterol levels accompanied with a down-regulation of PPARy expression and an up-regulation of GATA-3 expression. Berberine had no adverse effects on ND mice. These encouraging findings suggest that berberine has excellent pharmacological potential to prevent obesity.

Berberine increases expression of GAT-2 and GATA-3 during inhibition of adipocyte differentiation

Phytomedicine, 2009

It is known that a number of transcription factors are key regulators in the complex process of adipocyte differentiation including peroxisome proliferator activated receptor ? (PPAR?) and the CCAAT enhancer binding protein a (C/EBPa). Studies have demonstrated that in pre-adipocyte 3T3-L1 cells constitutive expression of the DNA binding proteins GATA-2 and GATA-3 results in protein/protein interactions with C/EBPa resulting in down-regulation of PPAR? and subsequent suppressed adipocyte differentiation with cells trapped at the pre-adipocyte stage. Thus it appears that GATA-2 and GATA-3 are of critical importance in regulating adipocyte differentiation through molecular interactions with PPAR? and C/EBPa. Recent reports suggest that berberine, an isoquinoline derivative alkaloid isolated from many medicinal herbs prevents differentiation of 3T3-L1 cells via a down regulation of PPAR? and C/EBPa expression. The aim of this study was to determine the effect of berberine on GATA-2 and -3 gene and protein expression levels during differentiation of 3T3-L1 cells. MTT (Methylthiazolyldiphenyl-tetrazolium bromide) was used to detect the cytotxic effects of berberine on the viability of 3T3-L1 cells during proliferation and differentiation. Differentiation of 3T3-L1 cells was monitored by Oil-Red-O staining and RT-PCR of PPAR? and C/EBPa and the expression of GATA-2 and -3 was determined by RT-PCR and Western Blot. Results show that following treatment with 8 µM berberine the mRNA and protein expression levels of GATA-2 and -3 were elevated and accompanied by inhibited adipocyte differentiation. These results may lead to the use of berberine to target the induction of specific genes such as GATA-2 and GATA-3 which affect adipocyte differentiation.

Using a commercially available DNA extraction kit to obtain high quality human genomic DNA suitable for PCR and genotyping from 11-year-old saliva saturated cotton spit pads

BMC Research Notes, 2008

Background: We sought to describe the integrity of human genomic DNA extracted from saliva saturated cotton spit wads stored at -20°C for approximately 11 years. 783 spit wad samples were collected from an ADHD sample population (Vermont Family Study) during 1996-2000. Human genomic DNA was extracted from the spit wads using a commercially available kit; QIAmp DNA Blood Midi Kit (Qiagen, Inc., Valencia, CA) with a few modifications.

Results: The resulting DNA yield was more that adequate for genetic analysis and ranged from approximately 1 µg to a total of 80 µg (mean 17.3 µgs ± 11.9 µgs). A260/A280 ratios for the human genomic DNA extracted from the spit wads was consistently within the generally acceptable values of 1.7-2.0, with the lowest purity being 1.70, and a mean value of 1.937 ± 0.226 for the 783 samples. The DNA also was suitable for PCR reactions as evidenced by the amplification of the serotonin-transporter-linked polymorphic region, 5HTTLPR. 5HTTLPR is a functional polymorphism in the promoter region of the serotonin transporter gene (HTT. SLC6A4, or SERT), consisting of two intensively studied alleles. 770 of the 783 samples (98.3%) produced fragments after PCR of the expected size with primers specific for 5HTTLPR.

Conclusion: High quality and abundant genomic DNA can be successfully retrieve from saliva saturated cotton spit wads using the commercially available kit, QIAmp DNA Blood Midi Kit from Qiagen, Inc. Furthermore, the DNA can be extracted in less than 3 hours and multiple samples can be processes simultaneously thus reducing processing time.

Identification of bidirectional promoters in the human KIR genes

Genes and Immunity, 2007

Although the class I MHC receptors expressed by human and mouse natural killer (NK) cells have distinct molecular origins, they are functional analogues that are expressed in a variegated pattern. The murine Ly49 calss I receptors contain bidirectional promoters that have been proposed to control the probabilistic expression of these genes. Whether similar elements are present in the human killer Ig-like receptor (KIR) genes is a fundamental question. A detailed analysis of the 2kb intergenic region separating the KIR2DL4 gene and the adjacent KIR3DL1 gene revealed that additional promoter elements exist in the human KIR genes. Remarkablly, the previously characterized KIR3DL1 proximal promoter possesses bidirectional promoter activity that maps to an 88 bp DNA fragment containing CREB, AML, Sp1 and Ets transcription factor binding sites. Individual KIR genes and alleles possess bidriectional promoters with distinct properties. Analysis of KIR+ and KIR- NK cells and NK precursors indicates that reverse transcripts from the bidirectional promoter are found in cells that lack KIR protein expression, but are not present in mature KIR-expressing NK cells, suggesting that reverse transcription from the proximal promoter blocks gene activation in immature NK and precursor cells.

Collaborative Publications

Identification of Common Genetic Variants Influencing Spontaneous Dizygotic Twinning and Female Fertility, American Journal of Human Genetics.

Mbarek H, Steinber S, Nyholt DR, Gordon SD, Miller MB, McRae AF, Hottenga JJ, Day FR, Willemsen G, de Geus EJC, Davies GE, Martin HC, Penninx BWJH, Jansen R, McAloney K, Vink JM, Kaprio J, Plomin R, Spector TD, Magnusson PK, Reversade B, Harris RA, Aagaard K, Kristjansson RP, Olafsson I, Eyjolfsson GI, Sigurdardottir O, Iacono WG, Lambalk CB, Montgomery GW, McGue M, Ong KK, Perry JRB, Martin NG, Stefansson H, Stefansson K, Boomsma D.

2016 May;98(5):898-908.

View the abstract.

Genetic and environmental influences interact with age and sex in shaping the human methylome, Nature Communications.

van Dongen J, Nivard MG, Willemsen G, Hottenga JJ, Helmer Q, Dolan CV, Ehli EA, Davies GE, van Iterson M, Breeze CE, Beck S, BIOS Consortium, Suchiman HE, Jansen R, van Meurs JB, Heijmans BT, Slagboom PE, Boomsma DI.

2016 April;7(11115):1-13.

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Genomic Landscape Established by Allelic Imbalance in the Cancerization Field of a Normal Appearing Airway, Cancer Research.

Jakubek YA, Lang W, Vattathil S, Garcia M, Xu L, Huang L, Lu W, Chow CW, Weber Z, Davies GE, Huang J, Behrens C, Kalhor N, Moran C, Fujimoto J, Mehran R, El-Zein R, Swisher S, Wang J, Fowler J, Spira A, Ehli EA, Wistuba II, Scheet P, Kadara H.

2016 Jul 1;76(13):3676-3683.

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Genomic Landscape of Colorectal Mucosa and Adenomas, Cancer Prevention Research.

Borras E, San Lucas FA, Chang K, Zhou R, Masand G, Fowler J, Mork ME, You YN, Taggart MW, McAllister F, Jones DA, Davies GE, Edelmann W, Ehli EA, Lynch PM, Hawk ET, Capella G, Scheet P, Vilar E.

2016 Jun;9(6):417-427.

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Minimally invasive genomic and transcriptomic profiling of visceral cancers by next-generation sequencing of circulating exosomes, Annals of Oncology.

San Lucas FA, Allenson K, Bernard V, Castillo J, Kim D, Ellis K, Ehli EA, Davies GE, Petersen JL, Li D, Wolff R, Katz M, Varadhachary G, Wistuba I, Maitra A, Alvarez H.

2016 Apr;27(4):635-641. Epub 2015 Dec 17.

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Intelligence: shared genetic basis between Mendelian disorders and a polygenic trait, European Journal of Human Genetics.

Franić S, Groen-Blokhuis MM, Dolan CV, Kattenberg MV, Pool R, Xiao X, Scheet PA, Ehli EA, Davies GE, van der Sluis S, Abdellaoui A, Hansell NK, Martin NG, Hudziak JJ, van Beijsterveldt CEM, Swagerman SC, Hulshoff Pol HE, de Geus EJC, Bartels M, Ropers HH, Hottenga JJ, Boomsma DI.

2015 Sept;23(10):1378-1383.

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Estimation of Genetic Relationships Between Individuals Across Cohorts and Platforms: Application to Childhood Height, Behavior Genetics.

Fedko IO, Hottenga JJ, Medina-Gomez C, Pappa I, van Beijsterveldt CE, Ehli EA, Davies GE, Rivadeneira F, Tiemeier H, Swertz MA, Middeldorp CM, Bartels M, Boomsma DI.

2015 Sept;45(5):514-528.

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Genetic Basis of a Cognitive Complexity Metric, PLoS ONE.

Hansell NK, Halford GS, Andrews G, Shum DHK, Harris SE, Davies G, Franic S, Christoforou A, Zietsch B, Painter J, Medland SE, Ehli EA, Davies GE, Steen VM, Lundervold AJ, Reinvang, Montgomery GW, Espeseth T, et al.

2015;10(4):e0123886.

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A genome-wide approach to children's aggressive behavior: The EAGLE Consortium, American Journal of Medical Genetics Part B: Neuropsychiatric Genetics.

Pappa I, St Pourcain B, Benke K, Cavadino A, Hakulinen C, Nivard MG, Nolte IM, Tiesler CM, Bakermans-Kranenburg MJ, Davies GE, Evans DM, Geoffroy MC, Grallert H, Groen-Blokhuis MM, Hudziak JJ, Kemp JP, Keltikangas-Järvinen L, McMahon G, Mileva-Seitz VR, Motazedi E, Power C, Raitakari OT, Ring SM, Rivadeneira F, Rodriguez A, Scheet PA, Seppälä I, Snieder H, Standl M, Thiering E, Timpson NJ, Veenstra R, Velders FP, Whitehouse AJ, Smith GD, Heinrich J, Hypponen E, Lehtimäki T, Middeldorp CM, Oldehinkel AJ, Pennell CE, Boomsma DI, Tiemeier H.

2016 Jul;171(5):562-572. Epub 2015 June 18.

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Common genetic variants influence human subcortical brain structures, Nature.

Hibar DP, Davies GE, Boomsma DI, Medland SE, et al.

2015 Apr 9;520(7546):224-229.

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Educational Attainment Influences Levels of Homozygosity through Migration and Assortative Mating, PLoS ONE.

Abdellaoui A, Hottenga JJ, Willemsen G, Bartels M, van Beijsterveldt T, Ehli EA, Davies GE, Brooks A, Sullivan PF, Penninx BWJH, de Geus EJ, Boomsma DI.

2015;10(3):e0118935.

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CNV Concordance in 1,097 MZ Twin Pairs. Twin Research and Human Genetics.

Abdellaoui A, Ehli E, Hottenga JJ, Weber Z, Mbarek H, Willemsen G, von Beijsterveldt T, Brooks A, Hudziak JJ, Sullivan PF, de Geus EJ, Davies GE, Boomsma DI.

2015 Feb;18(01):1-12.

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Mendelian and polygenic inheritance of intelligence: A common set of causal genes? Using next-generation sequencing to examine the effects of 168 intellectual disability genes on normal-range intelligence, Intelligence.

Franic S, Dolan CV, Broxholme J, Hu H, Zemojtel T, Davies GE, Nelson KA, Ehli EA, Pool R, Hottenga JJ, Childhood Intelligence Consortium, Ropers HH, Boomsma DI.

2015;49:10-22.

Attention Deficit Hyperactivity Disorder polygenic risk scores predict Attention Problems in a population-based sample of children, Journal of the American Academy of Child & Adolescent Psychiatry.

Groen-Blokhuis MM, Middeldorp CM, Kan K, Abdellaoui A, van Beijsterveldt CEM, Ehli EA, Davies GE, Scheet PA, Xiao X, Hudziak JJ, Hottenga J, Psychiatric Genomics Consortium ADHD Working Group, Neale BM, Boomsma DI.

2014 Oct;53(10):1123-9.

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Polygenic scores associated with educational attainment in adults predict educational achievement and attention problems in children, American Journal of Medical Genetics Part B: Neuropsychiatric Genetics.

de Zeeuw EL, van Beijsterveldt CEM, Glasner TJ, Ehli EA, Davies GE, Hudziak JJ, Social Science Genetic Association Consortium, Rietveld NA, Groen-Blokhuis MM, Hottenga J, de Geus EJC, Boomsma DI.

2014 Sep; 165(6):510-20.

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Genetic associations between intelligence and cortical thickness emerge at the start of puberty, Human Brain Mapping.

Brouwer RM, van Soelen IL, Swagerman SC, Schnack HG, Ehli EA, Kahn RS, Hulshoff Pol HE, and Boomsma DI.

2014 Aug;35(8):3760-73.

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A genome-wide association meta-analysis of preschool internalizing problems, Journal of the American Academy of Child & Adolescent Pschiatry.

Benke K, Nivard M, Velders F, Walters R, Pappa I, Scheet P, Xiao X, Ehli E, Palmer L, Whitehouse A, Verhulst F, Jaddoe V, Rivadeneira F, Groen-Blokhuis M, van Beijsterveldt C, Davies G, Hudziak J, Lubke G, Boomsma D, Pennell C, Tiemeier H, Middledorp C, Eagle Consortium.

2014 Jun;53(6):667-676.

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Epigenetic variation in monozygotic twins: A genome-wide analysis of DNA methylation in buccal cells, Genes.

van Dongen J, Ehli EA, Slieker RC, Bartels M, Weber ZM, Davies GE, Slagboom PE, Heijmans BT, Boomsma DI.

2014;5(2):347-65.

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Metformin and Berberine Prevent Olanzapine-Induced Weight Gain in Rats, PLoS One.

Hu Y, Young AJ, Ehli EA, Nowotny D, Davies PS, Droke EA, Soundy TJ, Davies GE.

2014;9(3):e93310. Epub 2014 Mar 25.

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The dopaminergic reward system and leisure time exercise behavior: a candidate allele study, BioMed Research International.

Huppertz C, Bartels M, Groen-Blokhuis M, Dolan C, de Moor M, Abdellaoui A, van Beijsterveldt T, Ehli EA, Hottenga J, Willemsen G, Xiao X, Scheet P, Davies G, Boomsma D, Hudziak J, de Geus E.

2014. Epub 2014 Mar 9.

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Association Between Autozygosity and Major Depression: Stratification Due to Religious Assortment, Behavior Genetics.

Abdellaoui A, Hottenga JJ, Xiao X, Scheet P, Ehli EA, Davies GE, Hudziak JJ, Smit DJA, Bartels M, Willemsen G, Brooks A, Sullivan PF, Smit JH, de Geus EJ, Phenninx BW, Boomsma D.

2013;43(6):455-467.

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Population structure, migration, and diversifying selection in the Netherlands, European Journal of Human Genetics.

Abdellaoui A, Hottenga JJ, Knijff PD, Nivard MG, Xiao X, Scheet P, Brooks A, Ehli EA, Hu Y, Davies GE, Hudziak JJ, Sullivan PF, van Beijsterveldt T, Willemsen G, de Geus EJ, Penninx BW, Boomsma DI.

2013 Mar 27. [Epub ahead of print]

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A prospective study of the effects of breastfeeding and FADS2 polymorphisms on cognition and hyperactivity/attention problems, American Journal of Medical Genetics Part B: Neuropsychiatric Genetics.

Groen-Blokhuis MM, Franic S, van Beijsterveldt CE, de Geus E, Bartels M, Davies GE, Ehli EA, Xiao X, Scheet PA, Althoff R, Hudziak JJ, Middeldorp CM, Boomsma DI.

2013 Jul;162(5):457-65.

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The Young Netherlands Twin Register (YNTR): Longitudinal Twin and Family Studies in Over 70,000 Children, Twin Research and Human Genetics.

van Beijsterveldt CE, Groen-Blokhuis M, Hottenga JJ, Franić S, Hudziak JJ, Lamb D, Huppertz C, de Zeeuw E, Nivard M, Schutte N, Swagerman S, Glasner T, van Fulpen M, Brouwer C, Stroet T, Nowotny D, Ehli EA,Davies GE, Scheet P, Orlebeke JF, Kan KJ, Smit D, Dolan CV, Middeldorp CM, de Geus EJ, Bartels M, Boomsma DI.

2013 Feb;16(1):252-67.

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Maternal prenatal smoking and offspring emotional problems: no moderating effect of maternal or child 5-HTTLPR genotype, American Journal of Medical Genetics Part B: Neuropsychiatric Genetics.

Geels LM, Groen-Blokhuis MM, van Beijsterveldt CE, Vink JM, Middeldorp CM, Bartels M, Nelson KA, Huizenga PE, Davies GE, Boomsma DI.
Maternal prenatal smoking and offspring emotional problems: no moderating effect of maternal or child 5-HTTLPR genotype. Am J Med Genet B Neuropsychiatr Genet.

2012 Dec;159B(8):1009-1012.

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Twins, tissue, and time: an assessment of SNPs and CNVs, Twin Research and Human Genetics.

Scheet P, Ehli EA, Xiao X, van Beijsterveldt CE, Abdellaoui A, Althoff RR, Hottenga JJ, Willemsen G, Nelson KA, Huizenga PE, Hu Y, Amos CI, Bartels M, Groen-Blokhuis MM, de Geus EJ, Hudziak JJ, Davies GE, Boomsma DI.

2012 Dec;15(6):737-45.

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De novo and inherited CNVs in MZ twin pairs selected for discordance and concordance on Attention Problems, European Journal of Human Genetics.

Ehli EA, Abdellaoui A, Hu Y, Hottenga JJ, Kattenberg M, van Beijsterveldt T, Bartels M, Althoff RR, Xiao X, Scheet P, de Geus EJ, Hudziak JJ, Boomsma DI, Davies GE.

2012 Oct;20(10):1037-1043.

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Lipid-lowering effect of berberine in human subjects and rats, Phytomedicine.

Hu Y, Ehli EA, Kittelsrud J, Ronan PJ, Munger K, Downey T, Bohlen K, Callahan L, Munson V, Jahnke M, Marshall LL, Nelson K, Huizenga P, Hansen R, Soundy TJ, Davies GE.

2012 Jul 15;19(10):861-867. Epub 2012 Jun 26.

View the abstract.

Genotyping performance between saliva and blood-derived genomic DNAs on the DMET array: a comparison, PLoS One.

Hu Y, Ehli EA, Nelson K, Bohlen K, Lynch C, Huizenga P, Kittelsrud J, Soundy TJ, Davies GE.

2012;7(3):e33968. Epub 2012 Mar 20.

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Identification and functional characterization of three novel alleles for the serotonin transporter-linked polymorphic region, Molecular Psychiatry.

Ehli EA, Hu Y, Lengyel-Nelson T, Hudziak JJ, Davies GE.

2012 Feb;17(2):185-192. Epub 2011 Jan 4.

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Associations among types of impulsivity, substance use problems and Neurexin-3 polymorphisms, Drug and Alcohol Dependence.

Stoltenberg SF, Lehmann MK, Christ CC, Hersrud SL, Davies GE.

2011 Dec 15;119(3):e31-38.

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Berberine and evodiamine influence serotonin transporter (5-HTT) expression via the 5-HTT-linked polymorphic region, Pharmacogenomics Journal.

Hu Y, Ehli EA, Hudziak JJ, Davies GE.

2012 Oct;12(5):372-378. Epub 2011 Jun 7.

View the abstract.

COMT Val158Met genotype as a risk factor for problem behaviors in youth, Journal of the American Academy of Child & Adolescent Psychiatry.

Albaugh MD, Harder VS, Althoff RR, Rettew DC, Ehli EA, Lengyel-Nelson T, Ayer L, Sulman J, Stanger C, Hudziak JJ.

2010 Aug;49(8):841-849. Epub 2010 Jul 1.

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Berberine inhibits SREBP-1-related clozapine and risperidone induced adipogenesis in 3T3-L1 cells, Phytotherapy Research.

Hu Y, Kutscher E, Davies GE.

2010 Dec;24(12):1831-1838.

View the abstract.

Pharmacogenomics: Has our history become modern medicine?, South Dakota Medicine.

Kutscher E, Davies GE.

2009 Apr;62(4):160-161.

Using a commercially available DNA extraction kit to obtain high quality human genomic DNA suitable for PCR and genotyping from 11-year-old saliva saturated cotton spit wads, BMC Research Notes.

Ehli EA, Lengyel-Nelson T, Hudziak JJ, Davies GE.

2008 Dec 22;1:133.

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