Genetic loci associated with an earlier age at onset in multiplex schizophrenia

Annemarie L Woolston; Po-Chang Hsiao; Po-Hsiu Kuo; Shi-Heng Wang; Yin-Ju Lien; Chih-Min Liu; Hai-Gwo Hwu; Tzu-Pin Lu; Eric Y Chuang; Li-Ching Chang; Chien-Hsiun Chen; Jer-Yuarn Wu; Ming T Tsuang; Wei J Chen

doi:10.1038/s41598-017-06795-8

Genetic loci associated with an earlier age at onset in multiplex schizophrenia

Sci Rep. 2017 Jul 25;7(1):6486. doi: 10.1038/s41598-017-06795-8.

Authors

Annemarie L Woolston¹, Po-Chang Hsiao², Po-Hsiu Kuo^{1

2

3}, Shi-Heng Wang^{1

4}, Yin-Ju Lien⁵, Chih-Min Liu^{6

7}, Hai-Gwo Hwu^{1

6}, Tzu-Pin Lu^{1

8}, Eric Y Chuang^{8

9}, Li-Ching Chang¹⁰, Chien-Hsiun Chen¹⁰, Jer-Yuarn Wu¹⁰, Ming T Tsuang^{11

12

13}, Wei J Chen^{14

15

16

17}

Affiliations

¹ National Taiwan University, College of Public Health, Institute of Epidemiology and Preventive Medicine, Taipei, 100, Taiwan.
² National Taiwan University, Genetic Epidemiology Core, Center of Genomic Medicine, Taipei, 100, Taiwan.
³ National Taiwan University, College of Public Health, Research Center of Genes, Environment, and Human Health, Taipei, 100, Taiwan.
⁴ China Medical University, Graduate Institute of Biostatistics, Taichung, 404, Taiwan.
⁵ National Taiwan Normal University, College of Education, College of Education, Department of Health Promotion and Health Education, Taipei, 106, Taiwan.
⁶ Department of Psychiatry, College of Medicine and National Taiwan University Hospital, National Taiwan University, Taipei, 100, Taiwan.
⁷ National Taiwan University Hospital, College of Medicine, Graduate Institute of Brain and Mind Sciences, National Taiwan University, Taipei, 100, Taiwan.
⁸ National Taiwan University, Center of Genomic Medicine, Bioinformatics and Biostatistics Core, Taipei, 100, Taiwan.
⁹ National Taiwan University, College of Electrical Engineering and Computer Science, Graduate Institute of Biomedical Electronics and Bioinformatics, Taipei, 106, Taiwan.
¹⁰ Academia Sinica, Institute of Biomedical Sciences, Taipei, 115, Taiwan.
¹¹ University of California, Center for Behavioral Genomics and Institute for Genomic Medicine, Department of Psychiatry, San Diego, 92093-0761, CA, USA.
¹² University of California, Department of Psychiatry, San Diego, 92093-0603, CA, USA.
¹³ Harvard Institute of Psychiatric Epidemiology and Genetics, Boston, 02115, MA, USA.
¹⁴ National Taiwan University, College of Public Health, Institute of Epidemiology and Preventive Medicine, Taipei, 100, Taiwan. wjchen@ntu.edu.tw.
¹⁵ National Taiwan University, Genetic Epidemiology Core, Center of Genomic Medicine, Taipei, 100, Taiwan. wjchen@ntu.edu.tw.
¹⁶ Department of Psychiatry, College of Medicine and National Taiwan University Hospital, National Taiwan University, Taipei, 100, Taiwan. wjchen@ntu.edu.tw.
¹⁷ National Taiwan University Hospital, College of Medicine, Graduate Institute of Brain and Mind Sciences, National Taiwan University, Taipei, 100, Taiwan. wjchen@ntu.edu.tw.

Abstract

An earlier age at onset (AAO) has been associated with greater genetic loadings in schizophrenia. This study aimed to identify modifier loci associated with an earlier AAO of schizophrenia. A genome-wide association analysis (GWAS) was conducted in 94 schizophrenia probands with the earliest AAO and 91 with the latest AAO. Candidate single nucleotide polymorphisms (SNPs) were then genotyped in the co-affected siblings and unrelated probands. Multi-SNP genetic risk scores (GRS) composed of the candidate loci were used to distinguish patients with an early or late AAO. The 14-SNP GRS could distinguish the co-affected siblings (n = 90) of the earliest probands from those (n = 91) of the latest probands. When 132 patients with an earlier AAO and 158 patients with a later AAO were included, a significant trend in the 14-SNP GRS was detected among those unrelated probands from 4 family groups with the earliest, earlier, later, and latest AAO. The overall effect of the 14 SNPs on an AAO in schizophrenia was verified using co-affected siblings of the GWAS probands and trend effect across unrelated patients. Preliminary network analysis of these loci revealed the involvement of PARK2, a gene intensively reported in Parkinson's disease and schizophrenia research.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Age of Onset
Aged
Case-Control Studies
Female
Genetic Loci*
Genetic Markers*
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide*
Schizophrenia / genetics*
Siblings

Substances

Genetic Markers