Family-based association study of ADHD and genes increasing the risk for smoking behaviours

2012 ◽  
Vol 97 (12) ◽  
pp. 1027-1033 ◽  
Author(s):  
Geeta A Thakur ◽  
Sarojini M Sengupta ◽  
Natalie Grizenko ◽  
Zia Choudhry ◽  
Ridha Joober
Keyword(s):  
Risk Allele ◽  
Clinical Sample ◽  
Smoking Behaviour ◽  
Common Mechanism ◽  
Large Sample Size ◽  
Nucleotide Polymorphisms ◽  
Children With Adhd ◽  
Risk Alleles ◽  
Externalising Behaviours ◽  
Family Based

ObjectiveTo investigate five top single nucleotide polymorphisms (SNPs) located in different genes and loci (CHRNA3, BDNF, DBH and LOC100188947) that were highly associated with different dimensions of smoking behaviour, in relation to attention-deficit hyperactivity disorder (ADHD).DesignCohort study consisting of a clinical sample of children with ADHD.SettingDouglas Institute ADHD Clinic, Montreal, Canada.PatientsFamilies of 454 children with ADHD aged 6–12 years old.InterventionsFamily-based association tests used to study the transmission of risk alleles within these five genetic markers.Main outcome measuresClinical diagnosis of ADHD, and a number of behavioural and neurocognitive phenotypes relevant to the disorder.ResultsOne SNP (rs1329650) from a non-coding RNA (LOC100188947) was significantly associated with overall ADHD diagnosis with the C* risk allele being over-transmitted from parents to children with ADHD (p=0.02). It was also over-transmitted to children with higher scores on Conners’ Parents (p=0.01) and Conners’ Teacher (p=0.002) index scores, and Child Behaviour Checklist withdrawn (p=0.001) and aggressive (p=0.007) behaviours. Children with poorer performances on executive and attention tasks were more likely to inherit the risk allele.ConclusionsThe C* allele of rs1329650 may be increasing the risk for ADHD and smoking behaviour through a common mechanism, possibly externalising behaviours and specific cognitive deficits that manifest as ADHD in childhood and are the gateway to smoking behaviour later in life. This exploratory study illustrates the use of comorbid disorders to investigate ADHD genetics. In spite of its relatively large sample size, replication in future studies is warranted.Trial Registration NumberNCT00483106.

Association Study of the Dystrobrevin-Binding Gene With Schizophrenia in Australian and Indian Samples

2006 ◽  
Vol 9 (4) ◽  
pp. 531-539 ◽  
Author(s):  
Elizabeth G. Holliday ◽  
Herlina Y. Handoko ◽  
Michael R. James ◽  
John J. McGrath ◽  
Deborah A. Nertney ◽  
...  
Keyword(s):  
Risk Allele ◽  
Risk Marker ◽  
Genotype Data ◽  
Nucleotide Polymorphisms ◽  
Hapmap Phase ◽  
Single Nucleotide ◽  
Risk Alleles ◽  
Sufficient Power ◽  
Allele Effect ◽  
Multiple Samples

AbstractNumerous studies have reported association between variants in the dystrobrevin binding protein 1 (dysbindin) gene (DTNBP1) and schizophrenia. However, the pattern of results is complex and to date, no specific risk marker or haplotype has been consistently identified. The number of single nucleotide polymorphisms (SNPs) tested in these studies has ranged from 5 to 20. We attempted to replicate previous findings by testing 16 SNPs in samples of 41 Australian pedigrees, 194 Australian cases and 180 controls, and 197 Indian pedigrees. No globally significant evidence for association was observed in any sample, despite power calculations indicating sufficient power to replicate several previous findings. Possible explanations for our results include sample differences in background linkage dis-equilibrium and/or risk allele effect size, the presence of multiple risk alleles upon different haplotypes, or the presence of a single risk allele upon multiple haplotypes. Some previous associations may also represent false positives. Examination of Caucasian HapMap phase II genotype data spanning theDTNBP1region indicates upwards of 40 SNPs are required to satisfactorily assess all nonredundant variation withinDTNBP1and its potential regulatory regions for association with schizophrenia. More comprehensive studies in multiple samples will be required to determine whether specificDTNBP1variants function as risk factors for schizophrenia.

scholarly journals Roma socioeconomic status has higher impact on smoking behaviour than genetic susceptibility

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
M A Merzah ◽  
P Pikó ◽  
R Ádány ◽  
S Fiatal
Keyword(s):  
Socioeconomic Status ◽  
Genetic Susceptibility ◽  
Risk Allele ◽  
Smoking Behaviour ◽  
Allele Frequencies ◽  
Risk Scores ◽  
Heavy Smoker ◽  
Nucleotide Polymorphisms ◽  
Cross Sectional ◽  
Smoking Behaviours

Abstract Background Prevalence of smoking in Hungarian Roma (HR) population is two to five times higher than in Hungarian general (HG) population. Our study aims to examine genetic susceptibility and other possible determinants associated to smoking behaviours in these populations. Methods A questionnaire based cross-sectional study was designed in HG (N = 412) and HR (N = 402) populations. Ten Single Nucleotide Polymorphisms (SNPs) were genotyped known to be robustly linked to smoking behaviours. Risk allele frequencies were compared. Additive genetic risk scores (unweighted GRS and weighted GRS) were constructed to compare genetic load from SNPs in genes NRXN1, CHRNA5/4, AGPHD1, MAOA, TRPC7, KCNJ6, GABRA4, and CYP2A6. Smoking behaviour were associated with GRSs and confounders (age, gender, BMI, socioeconomic status-SES) in several regression models. SES was calculated based on Modified Kuppuswamy scale 2019. Results Risk allele frequencies of four SNPs were found to be different between populations (p < 0.01). Median of GRS was equivalent among in populations; whilst wGRS median was slightly higher among Roma (5.2 compared to Hungarian 4.9; P = 0.02). In Roma both genders were more likely to be heavy smoker (OR = 2.05, 95%CI: 1.47-2.86; OR = 1.89, 95%CI: 1.58-2.25, for males and females, respectively) compared to counterparts from general population. GRS were higher among heavy smokers of both populations compared to other smoking behaviours (ORRoma= 1.06, 95%CI:0.98-1.15; ORHungarian=1.05, 95%CI=0.91-1.2). Strong reversible relationship was found between SES and smoking behaviours among study populations (p < 0.0001). Heavy, moderate, and former smokers were having lower SES compared to never smokers of both populations (SES β=-0.037, P = 0.04 for Hungarian; β=-0.039, P = 0.02 for Roma). Conclusions Socioeconomic status was shown as a priority indicator based on multifactorial regression analysis. The highest efforts should be focused on improving the SES of Roma population. Key messages Result of this study indicate the priority impact of SES instead of genetic susceptibility on Roma smoking behaviours variations. Interventions on improving socioeconomic status of the Roma might result in decreasing their cigarette consumption.

scholarly journals An Association Study of Interleukin 18 Receptor Genes (IL18R1 and IL18RAP) in Lumbar Disc Degeneration

2012 ◽  
Vol 6 (1) ◽  
pp. 164-171 ◽  
Author(s):  
Ahmad Omair ◽  
Benedicte Alexandra Lie ◽  
Olav Reikeras ◽  
Jens Ivar Brox
Keyword(s):  
Disc Degeneration ◽  
Risk Allele ◽  
Lumbar Disc ◽  
Significant Risk ◽  
Low Back ◽  
Nucleotide Polymorphisms ◽  
Interleukin 18 ◽  
Lumbar Disc Degeneration ◽  
Single Nucleotide ◽  
Risk Alleles

Objectives: To examine association of candidate genetic variants in structural, inflammatory, matrix modifying, vitamin D receptor genes and variants associated with osteoarthritis, with surgical candidates and surgical patients with lumbar disc degeneration (LDD), in light of their previously reported susceptibility for LDD. Methods: Genotyping of 146 Norwegian LDD patients and 188 Norwegian controls was performed for 20 single-nucleotide polymorphisms (SNPs) from collagen, aggrecan, interleukin, VDR, MMP3 and COX2 genes and 7 SNPs from osteoarthritic genes. Results: The neighboring genes IL18R1 and IL18RAP polymorphisms (rs2287037 and rs1420100), showed a statistically non-significant risk for developing LDD (OR 1.36 [95 % CI 0.99 – 1.87]; p=0.06 and OR 1.33 [95 % CI 0.98-1.81]; p=0.07). Homozygosity of these risk alleles was associated with LDD (p=0.023 and p=0.027). The non-risk alleles at these SNPs were situated on a haplotype negatively associated with LDD (p=0.008). Carriage of at least one non-risk allele at both loci also reduces the risk of developing LDD (OR 0.51 [95 % CI 0.33-0.80]; p=0.003). Conclusion: Our findings support the polygenic nature of LDD and suggest that variation in interleukin 18 receptor genes could affect the risk of severe LDD and associated low back pain.

scholarly journals A Phenome Wide Association Study of Severe COVID-19 Genetic Risk Variants

2021 ◽  
Author(s):  
Jessica A. Regan ◽  
Jawan Abdulrahim ◽  
Nathan Bihlmeyer ◽  
Carol Haynes ◽  
Lydia Coulter Kwee ◽  
...  
Keyword(s):  
Association Study ◽  
Genetic Risk ◽  
Risk Allele ◽  
Nucleotide Polymorphisms ◽  
Uk Biobank ◽  
Genetic Loci ◽  
Psoriatic Arthropathy ◽  
Risk Alleles ◽  
Atrial Fibrillation And Flutter ◽  
The Uk

AbstractBackgroundGenetic loci associated with risk of severe COVID-19 infection have been identified and individuals with complicated COVID-19 infections often have multiple comorbidities.ObjectiveIdentify known and unidentified comorbidities associated with genetic loci linked to risk of severe COVID-19 infection.MethodsA Phenome Wide Association Study (PheWAS) was conducted in 247,448 unrelated, white individuals from the UK Biobank to test the association of 1,402 unique phenotypes with ten genome-wide significant severe-COVID risk single nucleotide polymorphisms (SNP) identified from prior studies. A validation PheWAS was conducted in 2,247 white individuals from the CATHGEN.ResultsFour of the ten tested genetic loci showed significant phenotypic associations in UK Biobank after FDR adjustment. Vascular dementia significantly associated with rs7271165 near TMEM65 on 8q24.13 in individuals with the C risk allele (OR 5.66 [95% CI 2.21-11.85], q=0.049). We identified 40 novel phenotype associations with rs657152 on 9q34.2 coinciding with the ABO gene with individuals with the A COVID risk allele having higher odds of heart failure (OR 1.09 [95% CI 1.03-1.14], q=0.004), diabetes mellitus (OR 1.05 [95% CI 1.02-1.07], q=0.004) and hypercholesterolemia (OR 1.04 [95% CI 1.02-1.06], q=6.3×10−5). Eight phenotypes associated with rs1819040 near KANSL1 on 17q21.31 in individuals with the A risk allele including atrial fibrillation and flutter (OR 1.07 [95% CI 1.04-1.10], q=0.0084) and pulmonary fibrosis (OR 0.80 [95% CI 0.71-0.89], q=0.035). Ten novel phenotypic associations were identified in association with rs74956615 on 19p13.2 near the TYK2 gene including individuals with the A COVID risk allele having lower odds of psoriatic arthropathy (OR 0.31 [95% CI 0.20-0.47], q=4.5×10−5), rheumatoid arthritis (OR 0.83 [95% CI 0.64-0.83], p=1.4×10−6) and thyrotoxicosis with or without goiter (OR 0.77 [95% CI 0.68-0.87], p-6.9×10−5). Two associations for rs1819040 (KANSL1) and seven associations for rs74956615 (TYK2) validated in CATHGEN.ConclusionsUsing a broad PheWAS approach in a large discovery and validation cohort, we have identified novel phenotypic associations with risk alleles for severe COVID-19 infection. Interestingly, the ABO locus was associated with comorbidities that are also risk factors for severe COVID-19 infection, suggesting that this locus has pleiotropic effects and provides a potential mechanism for this association. The 19p13 locus was associated with lower risk of autoimmune disease, these findings may have broad implications for the importance of multiple comorbidities across both infectious and non-infectious diseases and may provide insight in the molecular function of the genes near these genetic risk loci.

scholarly journals Do Genetic Variants Modify the Effect of Smoking on Risk of Preeclampsia in Pregnancy?

2021 ◽  
Author(s):  
Anna E. Bauer ◽  
Christy L. Avery ◽  
Min Shi ◽  
Clarice R. Weinberg ◽  
Andrew F. Olshan ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Maternal Smoking ◽  
Risk Allele ◽  
Environment Interaction ◽  
Nucleotide Polymorphisms ◽  
Maternal Genotype ◽  
Family Based ◽  
Complex Relationships ◽  
Log Linear ◽  
Risk Of Preeclampsia

Objective Maternal smoking is associated with as much as a 50% reduced risk of preeclampsia, despite increasing risk of other poor pregnancy outcomes that often co-occur with preeclampsia, such as preterm birth and fetal growth restriction. Researchers have long sought to understand whether this perplexing association is biologically based, or a result of noncausal mechanisms. We examined whether smoking-response genes modify the smoking-preeclampsia association to investigate potential biological explanations. Study Design We conducted a nested case–control study within the Norwegian Mother, Father and Child Birth Cohort (1999–2008) of 2,596 mother–child dyads. We used family-based log-linear Poisson regression to examine modification of the maternal smoking-preeclampsia relationship by maternal and fetal single nucleotide polymorphisms involved in cellular processes related to components of cigarette smoke (n = 1,915 with minor allele frequency ≥10%). We further investigated the influence of smoking cessation during pregnancy. Results Three polymorphisms showed overall (p < 0.001) multiplicative interaction between smoking and maternal genotype. For rs3765692 (TP73) and rs10770343 (PIK3C2G), protection associated with smoking was reduced with two maternal copies of the risk allele and was stronger in continuers than quitters (interaction p = 0.02 for both loci, based on testing 3-level smoking by 3-level genotype). For rs2278361 (APAF1) the inverse smoking-preeclampsia association was eliminated by the presence of a single risk allele, and again the trend was stronger in continuers than in quitters (interaction p = 0.01). Conclusion Evidence for gene–smoking interaction was limited, but differences by smoking cessation warrant further investigation. We demonstrate the potential utility of expanded dyad methods and gene–environment interaction analyses for outcomes with complex relationships between maternal and fetal genotypes and exposures. Key Points

A Multimodal Assessment of Emotion Dysregulation in Young Children with and without ADHD

2020 ◽  
Author(s):  
Alexis Garcia ◽  
Anthony Dick ◽  
Paulo A. Graziano
Keyword(s):  
Young Children ◽  
Emotion Dysregulation ◽  
Clinical Sample ◽  
Children With Adhd ◽  
Callous Unemotional ◽  
Oppositional Defiant ◽  
Odd Symptoms ◽  
Final Sample ◽  
Discriminant Analyses ◽  
Multiple Domains

Objective: This study utilized a multimodal approach to examine emotion dysregulation (ED) in young children with attention-deficit/hyperactivity disorder (ADHD), ADHD + oppositional defiant disorder (ODD), and typically developing (TD) children. Methods: We sought to explore if specific domains of ED (emotion regulation [ER], negativity/lability [ERNL], emotion knowledge/understanding [ERU], and callous-unemotional [CU] behaviors) were uniquely associated with diagnostic classifications. The final sample consisted of 152 children (75% boys; mean age = 5.52, SD = .84, 83.4% Latinx) with the following group composition: ADHD- Only (n = 24), ADHD + ODD (n = 54), and TD (n = 74). Results: Higher levels of ADHD and ODD symptoms, measured continuously, were significantly associated with poorer EREG, greater ERNL, and higher levels of reported CU behaviors. There were no significant associations between ADHD or ODD symptoms on ERU. Using discriminant analyses, we found that parent/teacher reported EREG, ERNL, and CU were significant predictors of diagnostic classification. These ED domains correctly identified 84.7% of preschoolers. The model was most successful in classifying children with ADHD+ODD (92.3%) and TD (93.2%) children; however, the ADHD-Only group was correctly identified only 41.7% of the time. Conclusions: This is the first study to 1) examine multiple domains of ED in a clinical sample of preschool children with and without ADHD and 2) explore the clinical utility of considering ED when assessing for ADHD and ODD. Our findings suggest that measures of ED are particularly helpful for correctly diagnosing ADHD and co-occurring ODD but not necessarily children with ADHD-Only.

scholarly journals The Epidemiology and Genetics of Hyperuricemia and Gout across Major Racial Groups: A Literature Review and Population Genetics Secondary Database Analysis

2021 ◽  
Vol 11 (3) ◽  
pp. 231
Author(s):  
Faven Butler ◽  
Ali Alghubayshi ◽  
Youssef Roman
Keyword(s):  
Literature Review ◽  
Risk Allele ◽  
Statistical Significance ◽  
Elevated Serum ◽  
The United States ◽  
Allele Frequencies ◽  
Racial Groups ◽  
1000 Genomes Project ◽  
1000 Genomes ◽  
Risk Alleles

Gout is an inflammatory condition caused by elevated serum urate (SU), a condition known as hyperuricemia (HU). Genetic variations, including single nucleotide polymorphisms (SNPs), can alter the function of urate transporters, leading to differential HU and gout prevalence across different populations. In the United States (U.S.), gout prevalence differentially affects certain racial groups. The objective of this proposed analysis is to compare the frequency of urate-related genetic risk alleles between Europeans (EUR) and the following major racial groups: Africans in Southwest U.S. (ASW), Han-Chinese (CHS), Japanese (JPT), and Mexican (MXL) from the 1000 Genomes Project. The Ensembl genome browser of the 1000 Genomes Project was used to conduct cross-population allele frequency comparisons of 11 SNPs across 11 genes, physiologically involved and significantly associated with SU levels and gout risk. Gene/SNP pairs included: ABCG2 (rs2231142), SLC2A9 (rs734553), SLC17A1 (rs1183201), SLC16A9 (rs1171614), GCKR (rs1260326), SLC22A11 (rs2078267), SLC22A12 (rs505802), INHBC (rs3741414), RREB1 (rs675209), PDZK1 (rs12129861), and NRXN2 (rs478607). Allele frequencies were compared to EUR using Chi-Square or Fisher’s Exact test, when appropriate. Bonferroni correction for multiple comparisons was used, with p < 0.0045 for statistical significance. Risk alleles were defined as the allele that is associated with baseline or higher HU and gout risks. The cumulative HU or gout risk allele index of the 11 SNPs was estimated for each population. The prevalence of HU and gout in U.S. and non-US populations was evaluated using published epidemiological data and literature review. Compared with EUR, the SNP frequencies of 7/11 in ASW, 9/11 in MXL, 9/11 JPT, and 11/11 CHS were significantly different. HU or gout risk allele indices were 5, 6, 9, and 11 in ASW, MXL, CHS, and JPT, respectively. Out of the 11 SNPs, the percentage of risk alleles in CHS and JPT was 100%. Compared to non-US populations, the prevalence of HU and gout appear to be higher in western world countries. Compared with EUR, CHS and JPT populations had the highest HU or gout risk allele frequencies, followed by MXL and ASW. These results suggest that individuals of Asian descent are at higher HU and gout risk, which may partly explain the nearly three-fold higher gout prevalence among Asians versus Caucasians in ambulatory care settings. Furthermore, gout remains a disease of developed countries with a marked global rising.

scholarly journals Attachment Representation and Emotion Recognition Ability in Children with ADHD and Their Parents: A Study Protocol

2021 ◽  
Vol 18 (5) ◽  
pp. 2277
Author(s):  
Ruediger Kissgen ◽  
Sebastian Franke ◽  
Moritz Susewind ◽  
Maya Krischer
Keyword(s):  
Emotion Recognition ◽  
Clinical Sample ◽  
Disorganized Attachment ◽  
Control Group ◽  
Cross Sectional ◽  
Children With Adhd ◽  
Adhd Diagnosis ◽  
Attachment Research ◽  
Recognition Ability ◽  
Emotion Recognition Ability

Background: Few studies in clinical attachment research to date have examined children with an attention-deficit/hyperactivity disorder (ADHD) diagnosis. This is surprising for two reasons: first, there are a number of parallels between the behaviors of children with an insecure and disorganized attachment and the behaviors of children with an ADHD diagnosis. Second, secure attachment has a positive effect on the development of skills in areas in which children with ADHD demonstrate problems (e.g., attention span, impulse control). There are currently no findings on whether or not and how insecure and disorganized attachment and ADHD affect children’s emotion recognition ability. Methods: This is a cross-sectional study, part exploratory and part hypothesis-driven in the context of basic research. A clinical sample of 5- to 10-year-old children with an ADHD diagnosis and their parents is to be compared to a non-clinical unaffected control group. Over a period of 3 years, 80 subjects and their parents are to be recruited in each group for participation in the study. Discussion: This study is the first to examine links between attachment, emotion recognition ability, and ADHD. It is also the first to include not just children with ADHD but also their mothers and fathers in its design. The findings should help reduce the research gap and generate more knowledge for family interventions in the case of ADHD.

Role of the norepinephrine transporter polymorphisms in atomoxetine treatment: From response to side effects in children with ADHD

2021 ◽  
pp. 026988112110152
Author(s):  
Melike Kevser Gul ◽  
Elif Funda Sener ◽  
Muge Gulcihan Onal ◽  
Esra Demirci
Keyword(s):  
Side Effects ◽  
Treatment Response ◽  
Large Population ◽  
Norepinephrine Transporter ◽  
Response To Treatment ◽  
Nucleotide Polymorphisms ◽  
Children With Adhd ◽  
Real Time Quantitative Pcr ◽  
Treatment Side Effects ◽  
Adhd Treatment

Objective: Atomoxetine (ATX), one of the most commonly used drugs after stimulants in attention deficit hyperactivity disorder (ADHD) treatment, is an inhibitor of the norepinephrine transporter ( NET/SLC6A2), which is also associated with the etiology of ADHD. In this study, we aimed to investigate the effect of NET gene polymorphisms on response to ATX treatment and to find the answers to the questions about whether there is a relationship between the severity of the disorder and the observed side effects in children with ADHD. Method: About 100 children with ADHD and 80 healthy controls (HCs) were included in this study. The dose of ATX was started at 0.5 mg/kg/day and titrated at 1.2 mg/kg/day. Response to treatment of 78 patients was evaluated 2 months after the beginning of the treatment. After whole blood samples were obtained, DNAs were isolated, and samples were stored at −80°C. Two single-nucleotide polymorphisms (SNPs) (rs12708954 and rs3785143) were analyzed by real-time quantitative PCR (qRT-PCR). Results: The patients with both rs12708954 and rs3785143 heterozygous genotype had better treatment response and more side effects than patients with wild type. There was not found any association between any of the investigated NET polymorphisms and ADHD severity. Conclusion: It was, however, found that the NET rs12708954 and rs3785143 genotypes affect the treatment response to ATX in our study; thus, further studies with a large population are needed to understand the effects of NET polymorphisms on treatment, side effects, and also the severity of ADHD.

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