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- Garcia-Argibay, Miguel, 1988-, et al.
(författare)
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Attention deficit/hyperactivity disorder and major depressive disorder : evidence from multiple genetically informed designs
- 2024
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 95:5, s. 444-452
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) are two highly prevalent disorders that frequently co-occur. Prior evidence from genetic and cohort studies supports an association between ADHD and MDD. However, the direction and mechanisms underlying their association remain unclear. As ADHD onsets in early life, it has been hypothesized that ADHD may cause MDD.METHODS: In this study, we examined the association of ADHD with MDD using three different genetically informed methods to disentangle causality from confounding: 1) a nationwide longitudinal register-based full sibling comparison (N=1,018,489) adjusting for shared familial confounding; 2) a prospective co-twin control study comprising 16,447 twins (5,084 monozygotic and 11,393 dizygotic); and 3) a two-sample Mendelian randomization analysis using the largest available ADHD (N=225,534) and MDD (N=500,199) genome wide association (GWAS) summary statistics, adjusting for correlated and uncorrelated horizontal pleiotropy.RESULTS: Sibling and twin comparisons indicated that individuals with ADHD have an increased risk for subsequent development of MDD (HR=4.12 [3.62-4.69]) after adjusting for shared genetic and familial factors, and that ADHD scores endorsed by parents are positively associated with subsequent MDD scores at ages 15 and 18 years (b=0.07 [0.05-0.08]) and b=0.09 [0.08-0.11], respectively). Mendelian randomization analyses showed that genetic liability for ADHD is causally related to MDD (OR=1.15 [1.08-1.23]).CONCLUSIONS: Our study provided consistent results across three different genetically informative approaches, strengthening the hypothesis that ADHD is causally related to MDD.
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| 2. |
- Martin, Joanna, et al.
(författare)
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A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder
- 2018
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 83:12, s. 1044-1053
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is two to seven times more common in male individuals than in female individuals. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases.METHODS: We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (n = 20,183 cases, n = 35,191 controls) and Swedish population register data (n = 77,905 cases, n = 1,874,637 population controls).RESULTS: Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with r(g) estimates close to 1. Analyses of population data, however, indicated that female individuals with ADHD may be at especially high risk for certain comorbid developmental conditions (i.e., autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score analysis did not support a higher burden of ADHD common risk variants in female cases (odds ratio [confidence interval] = 1.02 [0.98-1.06], p = .28). In contrast, epidemiological sibling analyses revealed that the siblings of female individuals with ADHD are at higher familial risk for ADHD than the siblings of affected male individuals (odds ratio [confidence interval] = 1.14 [1.11-1.18], p = 1.5E-15).CONCLUSIONS: Overall, this study supports a greater familial burden of risk in female individuals with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence.
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