A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder
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A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder. / Martin, Joanna; Walters, Raymond K.; Demontis, Ditte; Mattheisen, Manuel; Lee, S. Hong; Robinson, Elise; Brikell, Isabell; Ghirardi, Laura; Larsson, Henrik; Lichtenstein, Paul; Eriksson, Nicholas; 23andMe Research Team; Psychiatric Genomics Consortium: ADHD Subgroup; iPSYCH–Broad ADHD Workgroup ; Werge, Thomas; Nordentoft, Merete.
I: Biological Psychiatry, Bind 83, Nr. 12, 15.06.2018, s. 1044-1053.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder
AU - Martin, Joanna
AU - Walters, Raymond K.
AU - Demontis, Ditte
AU - Mattheisen, Manuel
AU - Lee, S. Hong
AU - Robinson, Elise
AU - Brikell, Isabell
AU - Ghirardi, Laura
AU - Larsson, Henrik
AU - Lichtenstein, Paul
AU - Eriksson, Nicholas
AU - 23andMe Research Team
AU - Psychiatric Genomics Consortium: ADHD Subgroup
AU - iPSYCH–Broad ADHD Workgroup
AU - Werge, Thomas
AU - Nordentoft, Merete
PY - 2018/6/15
Y1 - 2018/6/15
N2 - 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 rg 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.
AB - 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 rg 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.
KW - ADHD
KW - Epidemiology
KW - GWAS
KW - Neurodevelopmental disorders
KW - Polygenic risk score analysis
KW - Sex bias
UR - http://www.scopus.com/inward/record.url?scp=85040102598&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2017.11.026
DO - 10.1016/j.biopsych.2017.11.026
M3 - Journal article
C2 - 29325848
AN - SCOPUS:85040102598
VL - 83
SP - 1044
EP - 1053
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
IS - 12
ER -
ID: 199170322