Genes & Genomics

, Volume 37, Issue 12, pp 1007–1016 | Cite as

Sex difference of autosomal alleles in populations of European and African descent

  • Lingjun Zuo
  • Tong Wang
  • Xiandong Lin
  • Jijun Wang
  • Yunlong Tan
  • Xiaoping WangEmail author
  • Xueqing Yu
  • Xingguang LuoEmail author
Research Article


In the present study, we aimed to report the individual sex-different genetic markers across autosomes in European- and African-origin populations. A total of 8400 females and 8081 males in 19 independent cohorts were genotyped across genomes using Illumina or Affymetrix arrays. The allele frequencies were compared between females and males in nine non-clean cohorts (with some human disease traits) using genome-wide logistic regression and then the nominally significant associations were replicated across 10 clean cohorts (without disease traits). Meta-analysis was performed to derive the combined p values across all cohorts. We found 13 markers that were genome-wide significant (p ≤ 5 × 10−8) between females and males in the meta-analysis of all cohorts of European descent, including rs7740449 at SYNE1, rs7531151 at PLD5, rs697455 at PPP1R12B, rs6745746 at LOC100128413, rs17000079 at PARM1, rs11948070 at PDE4D, rs7801825 at INSIG1, rs9551642 at MTUS2, rs2932174 at TPTE2, rs1961597 at SALL3, rs4117529 at METTL4, rs6021473 at SALL4 and rs6092466 at RAE1, and one marker, i.e., rs10145208 at PCNX, that was genome-wide significant in the meta-analysis of all cohorts of African descent. The most robust finding was rs7740449 at SYNE1, next to ESR1. We conclude that there are many sex-different markers on autosomes. These markers may be informative in differentiating females and males.


Sex-difference Autosome Allele European African Meta-analysis 



This work was supported in part by National Institute on Drug Abuse (NIDA) grant K01 DA029643, National Institute on Alcohol Abuse and Alcoholism (NIAAA) grants R21 AA021380, R21 AA020319 and R21 AA023237, the National Alliance for Research on Schizophrenia and Depression (NARSAD) Award 17616 (L.Z.) and ABMRF/The Foundation for Alcohol Research (L.Z.). We thank NIH GWAS Data Repository, the Contributing Investigator(s) who contributed the phenotype and genotype data from his/her original study (e.g., Drs. Bierut, Edenberg, Heath, Singleton, Hardy, Foroud, Myers, Gejman, Faraone, Sonuga-Barke, Sullivan, Nurnberger, Devlin, Monaco, etc.), and the primary funding organization that supported the contributing study. Funding and other supports for phenotype and genotype data were provided through the National Institutes of Health (NIH) Genes, Environment and Health Initiative (GEI) (U01HG004422, U01HG004436 and U01HG004438); the GENEVA Coordinating Center (U01HG004446); the NIAAA (U10AA008401, R01AA013320, P60AA011998); the NIDA (R01DA013423); the National Cancer Institute (P01 CA089392); the Division of Neuroscience, the NIA National Institute of Neurological Disorders and Stroke (NINDS); the NINDS Human Genetics Resource Center DNA and Cell Line Repository; the NIH contract “High throughput genotyping for studying the genetic contributions to human disease” (HHSN268200782096C); the Center for Inherited Disease Research (CIDR); a Cooperative Agreement with the Division of Adult and Community Health, Centers for Disease Control and Prevention; the NIH Office of Research on Women’s Health (ORWH) (R01NS45012); the Department of Veterans Affairs; the University of Maryland General Clinical Research Center (M01RR165001), the National Center for Research Resources, NIH; the National Institute of Mental Health (R01MH059160, R01MH59565, R01MH59566, R01MH59571, R01MH59586, R01MH59587, R01MH59588, R01MH60870, R01MH60879, R01MH61675, R01MH62873, R01MH081803, R01MH67257, R01MH81800, U01MH46276, U01MH46282, U01MH46289, U01MH46318, U01MH79469, U01MH79470 and R01MH67257); the NIMH Genetics Initiative for Bipolar Disorder; the Genetic Association Information Network (GAIN); the Genetic Consortium for Late Onset Alzheimer’s Disease; the Autism Genome Project, the MARC: Risk Mechanisms in Alcoholism and Comorbidity; the Molecular Genetics of Schizophrenia Collaboration; the Medical Research Council (G0601030) and the Wellcome Trust (075491/Z/04), University of Oxford; the Netherlands Scientific Organization (904-61-090, 904-61-193, 480-04-004, 400-05-717, NWO Genomics, SPI 56-464-1419) the Centre for Neurogenomics and Cognitive Research (CNCR-VU); Netherlands Study of Depression and Anxiety (NESDA) and the Netherlands Twin Register (NTR); and the European Union (EU/WLRT-2001-01254), ZonMW (geestkracht program, 10-000-1002). Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the Genetic Consortium for Late Onset Alzheimer’s Disease, the GENEVA Coordinating Center (U01 HG004446), and the National Center for Biotechnology Information. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research, and GlaxoSmithKline, R&D Limited. The datasets used for the analyses described in this manuscript were obtained from dbGaP at XL had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The financial sponsors had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

Compliance with ethical standards

Bioethical statement

All subjects gave written informed consent to participating in protocols approved by the relevant institutional review boards (IRBs). All subjects were de-identified in this study that was approved by Yale IRB.

Conflict of interest

The authors have declared that no competing interests exist.

Supplementary material

13258_2015_332_MOESM1_ESM.doc (68 kb)
Supplementary material 1 (DOC 67 kb)


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Copyright information

© The Genetics Society of Korea and Springer-Science and Media 2015

Authors and Affiliations

  • Lingjun Zuo
    • 1
    • 2
  • Tong Wang
    • 3
  • Xiandong Lin
    • 4
  • Jijun Wang
    • 5
  • Yunlong Tan
    • 6
  • Xiaoping Wang
    • 1
    • 7
    Email author
  • Xueqing Yu
    • 8
  • Xingguang Luo
    • 1
    • 2
    • 6
    Email author
  1. 1.Department of PsychiatryYale University School of MedicineNew HavenUSA
  2. 2.VA Connecticut Healthcare SystemWest HavenUSA
  3. 3.Department of Cellular and Molecular PhysiologyYale School of MedicineNew HavenUSA
  4. 4.Provincial Key Laboratory of Translational Cancer MedicineFujian Provincial Cancer HospitalFuzhouChina
  5. 5.Department of EEG & NeuroimagingShanghai Mental Health CenterShanghaiChina
  6. 6.Biological Psychiatry Research CenterBeijing Huilongguan HospitalBeijingChina
  7. 7.Department of Neurology, Shanghai First People’s HospitalShanghai Jiao-Tong UniversityShanghaiChina
  8. 8.Department of Nephrology, The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina

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