RT Journal Article
SR Electronic
T1 A genetic investigation of sex bias in the prevalence of attention deficit hyperactivity disorder
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 154088
DO 10.1101/154088
A1 Joanna Martin
A1 Raymond K. Walters
A1 Ditte Demontis
A1 Manuel Mattheisen
A1 S. Hong Lee
A1 Elise Robinson
A1 Isabell Brikell
A1 Laura Ghirardi
A1 Henrik Larsson
A1 Paul Lichtenstein
A1 Nicholas Eriksson
A1 23andme Research Team
A1 Psychiatric Genomics Consortium: ADHD Subgroup, iPSYCH-Broad ADHD Workgroup
A1 Thomas Werge
A1 Preben Bo Mortensen
A1 Marianne Giørtz Pedersen
A1 Ole Mors
A1 Merete Nordentoft
A1 David M. Hougaard
A1 Jonas Bybjerg-Grauholm
A1 Naomi Wray
A1 Barbara Franke
A1 Stephen V. Faraone
A1 Michael C. O’Donovan
A1 Anita Thapar
A1 Anders D. Børglum
A1 Benjamin M. Neale
YR 2017
UL http://biorxiv.org/content/early/2017/06/23/154088.abstract
AB Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is 2-7 times more common in males than females. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. We analyzed genome-wide common variants from the Psychiatric Genomics Consortium and iPSYCH Project (20,183 cases, 35,191 controls) and Swedish population-registry data (N=77,905 cases, N=1,874,637 population controls). We find strong genetic correlation for ADHD across sex and no mean difference in polygenic burden across sex. In contrast, siblings of female probands are at an increased risk of ADHD, compared to siblings of male probands. The results also suggest that females with ADHD are at especially high risk of comorbid developmental conditions. Overall, this study supports a greater familial burden of risk in females with ADHD and some clinical and etiological heterogeneity. However, autosomal common variants largely do not explain the sex bias in ADHD prevalence.