| 1. |
- Cortese, Samuele, et al.
(författare)
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Association between attention deficit hyperactivity disorder and asthma : a systematic review and meta-analysis and a Swedish population-based study
- 2018
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Ingår i: Lancet psychiatry. - : Elsevier. - 2215-0374 .- 2215-0366. ; 5:9, s. 717-726
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Forskningsöversikt (refereegranskat)abstract
- Background: Several studies have assessed the possible association between attention deficit hyperactivity disorder (ADHD) and asthma. However, existing evidence is inconclusive as to whether this association remains after controlling for possible important confounders. To fill this knowledge gap, we did a systematic review and meta-analysis, followed by a population-based study.Methods: For the systematic review and meta-analysis, we searched PubMed, PsycINFO, Embase, Embase Classic, Ovid MEDLINE, and Web of Knowledge databases up to Oct 31, 2017, for observational studies allowing estimation of the association between asthma and ADHD. No restrictions to date, language, or article type were applied. Unpublished data were collected from authors of the identified studies. We extracted unadjusted and adjusted odds ratios (ORs) from the identified studies and calculated ORs when they were not reported. We assessed study quality using the Newcastle-Ottawa Scale and study heterogeneity using I (2) statistics. A random-effects model was used to calculate pooled ORs. The systematic review is registered with PROSPERO (CRD42017073368). To address the fact that the ORs obtained in the meta-analysis were adjusted for confounders that inevitably varied across studies, we did a population-based study of individuals in multiple national registers in Sweden. We calculated an unadjusted OR and an OR that was simultaneously adjusted for all confounders identified in a directed acyclic graph based on the studies of asthma and ADHD identified in our systematic review.Findings: We identified 2649 potentially eligible citations, from which we obtained 49 datasets including a total of 210 363 participants with ADHD and 3 115 168 without. The pooled unadjusted OR was 1.66 (95% CI 1.22-2.26; I-2 = 99.47) and the pooled adjusted OR was 1.53 (1.41-1.65; I-2 = 50.76), indicating a significant association between asthma and ADHD. Possible lack of representativeness of the study population was detected with the Newcastle-Ottawa Scale in 42 of 49 datasets. In the population-based study, we included 1 575 377 individuals born between Jan 1, 1992, and Dec 31, 2006, of whom 259 253 (16.5%) had asthma and 57 957 (3.7%) had ADHD. Asthma was significantly associated with ADHD (OR 1.60, 95% CI 1.57-1.63) in the crude model adjusting for sex and year of birth, and this association remained significant after simultaneous adjustment for all covariates (1.45, 1.41-10.48).Interpretation: The combined results of the meta-analysis and the population-based study support a significant association between asthma and ADHD, which remained even after simultaneously controlling for several possible confounders in the population-based study. Awareness of this association might help to reduce delay in the diagnosis of both ADHD and asthma.
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| 2. |
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| 3. |
- Sun, Shihua, et al.
(författare)
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Association of Psychiatric Comorbidity With the Risk of Premature Death Among Children and Adults With Attention-Deficit/Hyperactivity Disorder
- 2019
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Ingår i: JAMA psychiatry. - : American Medical Association. - 2168-6238 .- 2168-622X. ; 76:11, s. 1141-1149
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Tidskriftsartikel (refereegranskat)abstract
- Importance: A previous register-based study reported elevated all-cause mortality in attention-deficit/hyperactivity disorder (ADHD), but cause-specific risks and the potential associations of psychiatric comorbidities remain unknown.Objectives: To investigate the all-cause and cause-specific mortality risks in ADHD and to explore the potential role of psychiatric comorbidities.Design, Setting, and Participants: This prospective cohort study used Swedish national registers to identify 2 675 615 individuals born in Sweden from January 1, 1983, through December 31, 2009, as the study population, among whom 86 670 individuals (3.2%) received a diagnosis of ADHD during follow-up. Follow-up was completed December 31, 2013, and data were analyzed from October 2018 through March 2019.Exposures: Attention-deficit/hyperactivity disorder identified by first clinical diagnosis or first prescription of ADHD medications as recorded in Swedish registers. Clinical diagnosis of psychiatric comorbidity was available in the National Patient Register.Main Outcomes and Measures: All-cause and cause-specific mortalities and hazard ratios (HRs) using Cox proportional hazards regression models.Results: In the overall cohort of 2 675 615 individuals, 1 374 790 (51.4%) were male (57 919 with an ADHD diagnosis) and 1 300 825 (48.6%) were female (28 751 with an ADHD diagnosis). Mean (SD) age at study entry was 6.4 (5.6) years. During follow-up, 424 individuals with ADHD and 6231 without ADHD died, resulting in mortality rates of 11.57 and 2.16 per 10 000 person-years, respectively. The association was stronger in adulthood (HR, 4.64; 95% CI, 4.11-5.25) compared with childhood (HR, 1.41; 95% CI, 0.97-2.04) and increased substantially with the number of psychiatric comorbidities with ADHD (HR for individuals with only ADHD, 1.41 [95% CI, 1.01-1.97]; HR for those with ≥4 comorbidities, 25.22 [95% CI, 19.60-32.46]). In adulthood, when adjusting for early-onset psychiatric comorbidity, the association between ADHD and risk of death due to natural causes was attenuated substantially and was no longer statistically significant (HR, 1.32; 95% CI, 0.94-1.85). When adjusting for later-onset psychiatric disorders, the association was attenuated to statistical nonsignificance for death due to suicide (HR, 1.13; 95% CI, 0.88-1.45) but remained statistically significant for death caused by unintentional injury (HR, 2.14; 95% CI, 1.71-2.68) or other external causes (HR, 1.75; 95% CI, 1.23-2.48).Conclusions and Relevance: Psychiatric comorbidity appears to play an important role in all-cause and cause-specific mortality risks in ADHD. In adulthood, early-onset psychiatric comorbidity contributed primarily to the association with death due to natural causes, whereas later-onset psychiatric comorbidity mainly influenced death due to unnatural causes, including suicide and unintentional injury. These findings suggest that health care professionals should closely monitor specific psychiatric comorbidities in individuals with ADHD to identify high-risk groups for prevention efforts.
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| 4. |
- Sun, Shihua
(författare)
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Attention-deficit/hyperactivity disorder and adverse health outcomes : from association to prevention
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed neurodevelopmental disorder, characterized by persistent inattention and/or hyperactivity-impulsivity that are inappropriate for one’s developmental stage. Individuals with ADHD suffer from adverse outcomes including somatic and psychiatric comorbidities. ADHD is also associated with increased risk of factors that may impose higher mortality risks. However, evidence has been limited on the association between ADHD and somatic diseases such as asthma. Also, the association between ADHD and premature death, as well as the potential effects of ADHD medication treatment is largely unknown. The overarching aim of this thesis is to investigate the associations between ADHD and specific adverse outcomes including asthma and premature death. Individual studies were conducted to clarify the magnitude and etiology of the associations, as well as potential effects from medication treatment that may prevent poor prognosis. In Study I, we combined a meta-analysis of existing studies and a Swedish national population-based analysis to investigate the population-level association between asthma and ADHD. In the meta-analysis, we found a significant cross-sectional association between asthma and ADHD when considering both unadjusted and adjusted odds ratios. The sub-group and meta-regression analyses showed consistently robust results across study settings. Estimates of the association from the Swedish population analysis were similar with the pooled results from the meta-analysis, and the association remained statistically significant after adjustment of potential confounders in the population-based analysis. In Study II, we investigated the familial liability to the comorbidity between asthma and ADHD. In the familial co-aggregation analysis, relatives of individuals with asthma had an increased risk of ADHD compared to relatives of individuals without asthma. The association was strongest in monozygotic twins and attenuated with decreasing degree of genetic relatedness. Results from the twin modelling analysis supported that a substantial part of the association between asthma and ADHD was explained by genetic factors. Estimates for contributions from shared and non-shared environment factors were not statistically significant. In Study III, we investigated the all-cause and cause-specific mortality risks in ADHD and the role of psychiatric comorbidity. We found that ADHD was associated with significantly increased all-cause and cause-specific mortality risks, with suicide and unintentional injuries being the leading causes of death. Psychiatric comorbidity largely mediated the elevated mortality risks in ADHD, as the mortality risks increased substantially with the number of comorbid psychiatric disorders. Early-onset disorders such as conduct disorders contributed substantially to the association for natural deaths, while later-onset disorders such as substance use disorders may have mediated most of the risk for unnatural deaths in ADHD. In Study IV, we investigated how ADHD medication initiation and continuation associated with mortality risks among individuals with ADHD. During follow-up to a maximum of 2 years, the mortality rates due to any cause and unnatural causes were significantly lower among those who initiated medication treatment compared to those who had not initiated medication. Among individuals who had been on ADHD medication for up to 6 months after diagnosis, continuation of medication treatment was significantly associated with substantially lower all-cause and unnatural cause-specific mortality risks including suicide and unintentional injuries compared to discontinuation. In summary, results of Study I and II together support the significant association between asthma and ADHD. The comorbidity may largely be explained by shared etiology, with substantial influences from shared genetic factors. The findings also point out shared genetic factors as an important direction to understand the mechanisms of adverse conditions related to ADHD other than asthma. Study III and IV together reveal that ADHD is associated with significantly increased all-cause and cause-specific mortality risks, and ADHD medication treatment may help to reduce the risks. The findings point out medication treatment as a promising way to prevent extremely severe adverse outcomes among individuals with ADHD. In conclusion, findings from this thesis work support that individuals with ADHD are at increased risk of adverse outcomes including somatic conditions such as asthma and severe adversities such as premature death. Shared genetic factors largely explained the association between asthma and ADHD, indicating the significance of detecting within-individual and family history of either disorder for preventing delayed diagnosis of the other condition. Moreover, psychiatric comorbidities and medication treatment play crucial roles in understanding the mechanisms of ADHD associated mortality risks and in preventing premature deaths among individuals with ADHD.
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| 5. |
- Sun, Shihua, et al.
(författare)
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Family co-aggregation of asthma and ADHD : a Swedish register-based study
- 2019
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Ingår i: Behavior Genetics. - : Springer. - 0001-8244 .- 1573-3297. ; 49:6, s. 512-512
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- A significant cross-sectional association between asthma and ADHD was reported from a recent meta-analysis and population based study. Asthma and ADHD both aggregate in families, but whether and to what extent the phenotypic association can be explained by familial liability remain unknown. In this Swedish national register-based study, we investigated how asthma and ADHD co-aggregate within individuals and within families to test for the shared familial liability. We studied 2 714 000 individuals born in Sweden between 1983 and 2009, and extracted clinical diagnosis records of asthma and ADHD from Swedish registers. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) the association between clinically diagnosed asthma and ADHD both within individuals and families. Individuals with asthma had higher risk of having ADHD compared to individuals without asthma (OR = 1.85, 95% CI 1.81–1.90). Within families, the association was stronger in monozygotic twins (OR = 1.96, 95% CI 1.25–3.07) than in dizygotic twins (OR = 1.62, 95% CI 1.36–1.92), full-siblings (OR = 1.50, 95% CI 1.46–1.55), maternal-half siblings (OR = 1.27, 95% CI 1.21–1.32), paternal half-siblings (OR = 1.11, 95% CI 1.06–1.16), full-cousins (OR = 1.12, 95% CI 1.10–1.14) and half-cousins (OR = 1.06, 95% CI 1.03–1.09). The pattern of associations estimated from different degrees of relatives supports shared familial liability, especially genetic overlap, underlying clinically diagnosed asthma and ADHD.
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| 6. |
- Wang, Juan, et al.
(författare)
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GWAS Discovery Of Candidate Genes for Yield-Related Traits in Peanut and Support from Earlier QTL Mapping Studies
- 2019
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Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- Peanut (Arachishypogaea L.) is one of the most important oil crops worldwide, and its yet increasing market demand may be met by genetic improvement of yield related traits, which may be facilitated by a good understanding of the underlying genetic base of these traits. Here, we have carried out a genome-wide association study (GWAS) with the aim to identify genomic regions and the candidate genes within these regions that may be involved in determining the phenotypic variation at seven yield-related traits in peanut. For the GWAS analyses, 195 peanut accessions were phenotyped and/or genotyped; the latter was done using a genotyping-by-sequencing approach, which produced a total of 13,435 high-quality single nucleotide polymorphisms (SNPs). Analyses of these SNPs show that the analyzed peanut accessions can be approximately grouped into two big groups that, to some extent, agree with the botanical classification of peanut at the subspecies level. By taking this genetic structure as well as the relationships between the analyzed accessions into consideration, our GWAS analyses have identified 93 non-overlapping peak SNPs that are significantly associated with four of the studied traits. Gene annotation of the genome regions surrounding these peak SNPs have found a total of 311 unique candidate genes. Among the 93 yield-related-trait-associated SNP peaks, 12 are found to be co-localized with the quantitative trait loci (QTLs) that were identified by earlier related QTL mapping studies, and these 12 SNP peaks are only related to three traits and are almost all located on chromosomes Arahy.05 and Arahy.16. Gene annotation of these 12 co-localized SNP peaks have found 36 candidates genes, and a close examination of these candidate genes found one very interesting gene (arahy.RI9HIF), the rice homolog of which produces a protein that has been shown to improve rice yield when over-expressed. Further tests of the arahy.RI9HIF gene, as well as other candidate genes especially those within the more confident co-localized genomic regions, may hold the potential for significantly improving peanut yield.
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| 7. |
- Wang, Juan, et al.
(författare)
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Identification of Quantitative Trait Nucleotides and Development of Diagnostic Markers for Nine Fatty Acids in the Peanut
- 2024
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Ingår i: Plants. - 2223-7747. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- The cultivated peanut (Arachis hypogaea L.) is an important oilseed crop worldwide, and fatty acid composition is a major determinant of peanut oil quality. In the present study, we conducted a genome-wide association study (GWAS) for nine fatty acid traits using the whole genome sequences of 160 representative Chinese peanut landraces and identified 6-1195 significant SNPs for different fatty acid contents. Particularly for oleic acid and linoleic acid, two peak SNP clusters on Arahy.09 and Arahy.19 were found to contain the majority of the significant SNPs associated with these two fatty acids. Additionally, a significant proportion of the candidate genes identified on Arahy.09 overlap with those identified in early studies, among which three candidate genes are of special interest. One possesses a significant missense SNP and encodes a known candidate gene FAD2A. The second gene is the gene closest to the most significant SNP for linoleic acid. It codes for an MYB protein that has been demonstrated to impact fatty acid biosynthesis in Arabidopsis. The third gene harbors a missense SNP and encodes a JmjC domain-containing protein. The significant phenotypic difference in the oleic acid/linoleic acid between the genotypes at the first and third candidate genes was further confirmed with PARMS analysis. In addition, we have also identified different candidate genes (i.e., Arahy.ZV39IJ, Arahy.F9E3EA, Arahy.X9ZZC1, and Arahy.Z0ELT9) for the remaining fatty acids. Our findings can help us gain a better understanding of the genetic foundation of peanut fatty acid contents and may hold great potential for enhancing peanut quality in the future.
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| 8. |
- Wang, Juan, et al.
(författare)
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The genetic base for peanut height-related traits revealed by a meta-analysis
- 2021
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Ingår i: Plants. - : MDPI AG. - 2223-7747. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Peanut (Arachis hypogaea L.) is an important oilseed crop worldwide, and peanut height has been shown to be closely related to yield, therefore a better understanding of the genetic base of plant height-related traits may allow us to have better control of crop yield. Plant height-related traits are quantitative traits that are genetically controlled by many genes, and distinct quantitive trait loci (QTLs) may be identified for different peanut accessions/genotypes. In the present study, in order to gain a more complete picture of the genetic base for peanut height-related traits, we first make use of the high quality NGS sequence data for 159 peanut accessions that are available within our research groups, to carry out a GWAS study for searching plant height-related regions. We then perform a literature survey and collect QTLs for two plant height-related traits (Ph: peanut main stem height, and Fbl: the first branch length) from earlier related QTL/GWAS studies in peanut. In total, we find 74 and 21 genomic regions that are, associated with traits Ph and Fbl, respectively. Annotation of these regions found a total of 692 and 229 genes for, respectively, Ph and Fbl, and among those genes, 158 genes are shared. KEGG and GO enrichment analyses of those candidate genes reveal that Ph-and Fbl-associated genes are both enriched in the biosynthesis of secondary metabolites, some basic processes, pathways, or complexes that are supposed to be crucial for plant development and growth.
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| 9. |
- Wang, Juan, et al.
(författare)
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Twelve complete chloroplast genomes of wild peanuts : great genetic resources and a better understanding of Arachis phylogeny
- 2019
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Ingår i: BMC Plant Biology. - : Springer Science and Business Media LLC. - 1471-2229. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The cultivated peanut (Arachis hypogaea) is one of the most important oilseed crops worldwide, however, its improvement is restricted by its narrow genetic base. The highly variable wild peanut species, especially within Sect. Arachis, may serve as a rich genetic source of favorable alleles to peanut improvement; Sect. Arachis is the biggest taxonomic section within genus Arachis and its members also include the cultivated peanut. In order to make good use of these wild resources, the genetic bases and the relationships of the Arachis species need first to be better understood. RESULTS: Here, in this study, we have sequenced and/or assembled twelve Arachis complete chloroplast (cp) genomes (eleven from Sect. Arachis). These cp genome sequences enriched the published Arachis cp genome data. From the twelve acquired cp genomes, substantial genetic variation (1368 SNDs, 311 indels) has been identified, which, together with 69 SSR loci that have been identified from the same data set, will provide powerful tools for future explorations. Phylogenetic analyses in our study have grouped the Sect. Arachis species into two major lineages (I & II), this result together with reports from many earlier studies show that lineage II is dominated by AA genome species that are mostly perennial, while lineage I includes species that have more diverse genome types and are mostly annual/biennial. Moreover, the cultivated peanuts and A. monticola that are the only tetraploid (AABB) species within Arachis are nested within the AA genome species-dominated lineage, this result together with the maternal inheritance of chloroplast indicate a maternal origin of the two tetraploid species from an AA genome species. CONCLUSION: In summary, we have acquired sequences of twelve complete Arachis cp genomes, which have not only helped us better understand how the cultivated peanut and its close wild relatives are related, but also provided us with rich genetic resources that may hold great potentials for future peanut breeding.
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