@article{c61cac2bc4044a66b488c21cd573e6e2,
title = "Quantifying between-cohort and between-sex genetic heterogeneity in major depressive disorder",
abstract = "Major depressive disorder (MDD) is clinically heterogeneous with prevalence rates twice as high in women as in men. There are many possible sources of heterogeneity in MDD most of which are not measured in a sufficiently comparable way across study samples. Here, we assess genetic heterogeneity based on two fundamental measures, between-cohort and between-sex heterogeneity. First, we used genome-wide association study (GWAS) summary statistics to investigate between-cohort genetic heterogeneity using the 29 research cohorts of the Psychiatric Genomics Consortium (PGC; N cases = 16,823, N controls = 25,632) and found that some of the cohort heterogeneity can be attributed to ascertainment differences (such as recruitment of cases from hospital vs. community sources). Second, we evaluated between-sex genetic heterogeneity using GWAS summary statistics from the PGC, Kaiser Permanente GERA, UK Biobank, and the Danish iPSYCH studies but did not find convincing evidence for genetic differences between the sexes. We conclude that there is no evidence that the heterogeneity between MDD data sets and between sexes reflects genetic heterogeneity. Larger sample sizes with detailed phenotypic records and genomic data remain the key to overcome heterogeneity inherent in assessment of MDD.",
keywords = "LD score regression, MDD, depression, genetic heterogeneity, sex differences",
author = "{Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium} and Maciej Trzaskowski and Divya Mehta and Peyrot, {Wouter J.} and David Hawkes and Daniel Davies and Howard, {David M.} and Kemper, {Kathryn E.} and Julia Sidorenko and Robert Maier and Stephan Ripke and Manuel Mattheisen and Baune, {Bernhard T.} and Grabe, {Hans J.} and Heath, {Andrew C.} and Lisa Jones and Ian Jones and Madden, {Pamela A.F.} and McIntosh, {Andrew M.} and Gerome Breen and Lewis, {Cathryn M.} and B{\o}rglum, {Anders D.} and Sullivan, {Patrick F.} and Martin, {Nicholas G.} and Kendler, {Kenneth S.} and Levinson, {Douglas F.} and Wray, {Naomi R.}",
note = "Funding Information: information National Health & Medical Research Council, Award Numbers: 1087889, 1113400, 1078901We acknowledge funding from the Australian National Health & Medical Research Council (1078901, 1113400, and 1087889). The PGC has received major funding from the US National Institute of Mental Health and the US National Institute on Drug Abuse (U01 MH109528 and U01 MH1095320). A full list of funding is provided in Wray et al. (). UK Biobank: this research has been conducted using the UK Biobank 593 Resource (URLs), including applications #4844 and #6818. The Genetic Epidemiology Research on Adult Health and Aging (GERA) study was supported by grant RC2 AG036607 from the National Institute of Health, grants from Robert Wood Johnson Foundation, the Ellison Medical Foundation, the Wayne and Gladys Valley Foundation, and Kaiser Permanente. The authors thank the Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) members who have generously agreed to participate in the Kaiser Permanente Research Program on Genes, Environment and Health (RPGEH). Funding Information: We acknowledge funding from the Australian National Health & Medical Research Council (1078901, 1113400, and 1087889). The PGC has received major funding from the US National Institute of Mental Health and the US National Institute on Drug Abuse (U01 MH109528 and U01 MH1095320). A full list of funding is provided in Wray et al. (2018). UK Biobank: this research has been conducted using the UK Biobank 593 Resource (URLs), including applications #4844 and #6818. The Genetic Epidemiology Research on Adult Health and Aging (GERA) study was supported by grant RC2 AG036607 from the National Institute of Health, grants from Robert Wood Johnson Foundation, the Ellison Medical Foundation, the Wayne and Gladys Valley Foundation, and Kaiser Permanente. The authors thank the Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) members who have generously agreed to participate in the Kaiser Permanente Research Program on Genes, Environment and Health (RPGEH). Publisher Copyright: {\textcopyright} 2019 Wiley Periodicals, Inc.",
year = "2019",
month = sep,
doi = "10.1002/ajmg.b.32713",
language = "English",
volume = "180",
pages = "439--447",
journal = "American Journal of Medical Genetics - Neuropsychiatric Genetics",
issn = "1552-4841",
number = "6",
}