Investigating the causal risk factors for self-harm by integrating Mendelian randomisation within twin modelling

TY - JOUR

T1 - Investigating the causal risk factors for self-harm by integrating Mendelian randomisation within twin modelling

AU - Lim, Kai Xiang

AU - Oginni, Olakunle Ayokunmi

AU - Rimfeld, Kaili

AU - Pingault, Jean Baptiste

AU - Rijsdijk, Frühling

N1 - Funding Information: KXL is supported by King’s International Postgraduate Research Scholarship. OAO is supported by the Commonwealth Scholarship (Award No: NGCA-2018-65), a global scholarship programme funded by the Foreign and Commonwealth Office, United Kingdom. JBP is supported by the Medical Research Foundation 2018 Emerging Leaders 1st Prize in Adolescent Mental Health (MRF-160-0002-ELP-PINGA). KR is supported by a Sir Henry Wellcome Postdoctoral Fellowship. Funding Information: TEDS is supported by a programme grant to Professor Robert Plomin from the UK Medical Research Council (MR/V012878/1 and previously MR/M021475/1), with additional support from the US National Institutes of Health (AG046938). We gratefully acknowledge the ongoing contribution of the participants in the Twins Early Development Study (TEDS) and their families. Publisher Copyright: © 2022, The Author(s).

PY - 2022/11

Y1 - 2022/11

N2 - Previous genetically informed studies have uncovered likely causal relationships between mental health problems and self-harm but resulting causal estimates may be biased due to unmediated pleiotropy. By fitting Mendelian Randomization - Direction of Causation (MR-DoC) models that explicitly model pleiotropy, we investigated the effect of four quantitatively measured mental health problems - major depressive disorder (MDD), schizophrenia, attention-deficit hyperactivity disorder (ADHD), and insomnia, on non-suicidal self-harm (NSSH) and suicidal self-harm (SSH), separately. We used data of 12,723 twins (56.6% females) in the Twins Early Development Study. Besides substantial pleiotropy, we found effects from child-rated depressive symptoms to both NSSH (β = 0.194, 95% CIs: 0.131, 0.257) and SSH (β = 0.210, 95% CIs: 0.125, 0.295). Similarly, effects flowed from parent-rated depressive symptoms to NSSH (β = 0.092, 95% CIs: 0.004, 0.181) and SSH (β = 0.165, 95% CIs: 0.051, 0.281). We did not find evidence of aetiological difference between NSSH and SSH.

AB - Previous genetically informed studies have uncovered likely causal relationships between mental health problems and self-harm but resulting causal estimates may be biased due to unmediated pleiotropy. By fitting Mendelian Randomization - Direction of Causation (MR-DoC) models that explicitly model pleiotropy, we investigated the effect of four quantitatively measured mental health problems - major depressive disorder (MDD), schizophrenia, attention-deficit hyperactivity disorder (ADHD), and insomnia, on non-suicidal self-harm (NSSH) and suicidal self-harm (SSH), separately. We used data of 12,723 twins (56.6% females) in the Twins Early Development Study. Besides substantial pleiotropy, we found effects from child-rated depressive symptoms to both NSSH (β = 0.194, 95% CIs: 0.131, 0.257) and SSH (β = 0.210, 95% CIs: 0.125, 0.295). Similarly, effects flowed from parent-rated depressive symptoms to NSSH (β = 0.092, 95% CIs: 0.004, 0.181) and SSH (β = 0.165, 95% CIs: 0.051, 0.281). We did not find evidence of aetiological difference between NSSH and SSH.

KW - Direction of Causation

KW - Mendelian randomisation

KW - Mental health

KW - MR-DoC

KW - non-suicidal self-harm

KW - suicidal self-harm

UR - http://www.scopus.com/inward/record.url?scp=85138313636&partnerID=8YFLogxK

U2 - 10.1007/s10519-022-10114-x

DO - 10.1007/s10519-022-10114-x

M3 - Article

C2 - 36103101

AN - SCOPUS:85138313636

SN - 0001-8244

VL - 52

SP - 324

EP - 337

JO - Behavior Genetics

JF - Behavior Genetics

IS - 6

ER -