<abstract xmlns="http://www.w3.org/1999/xhtml"><p>Depression is estimated to affect 350 million people worldwide. The World Mental Health Survey conducted in 17 countries found that, on average, about one in 20 people reported having an episode of depression in the previous year. Although depression has been shown to be moderately heritable by studies conducted in the past, the search for its so-called missing heritability has so far been unsuccessful. The difficulty in identifying common genetic variants predisposing to depression could be due to large sample sizes needed to detect small effects on genetic risk and the heterogeneous nature of major depressive disorder (MDD). The aim of our study was to determine whether there was a connection between a family history of depression in MDD patients and the presence of putative risk variants in the well-studied <italic>SLC6A4</italic>, <italic>COMT</italic> and <italic>PCLO</italic> genes. We analyzed 133 patients with MDD (30.0% with a positive family history for MDD and 70.0% sporadic cases) and compared them to 279 healthy controls. When comparing all the depressed patients to controls, no significant differences in genotype and allele distributions were detected. After stratifying patients according to their family history, the <italic>PCLO</italic> rs2522833 C allele was shown to be significantly less common in patients with a positive family history (<italic>p</italic> = 0.001), indicating a possible difference in the genetic structure of MDD between familial and sporadic cases and a less important role of the common genetic risk variants for the development of MDD in familial cases.</p></abstract>

Depression is estimated to affect 350 million people worldwide. The World Mental Health Survey conducted in 17 countries found that, on average, about one in 20 people reported having an episode of depression in the previous year. Although depression has been shown to be moderately heritable by studies conducted in the past, the search for its so-called missing heritability has so far been unsuccessful. The difficulty in identifying common genetic variants predisposing to depression could be due to large sample sizes needed to detect small effects on genetic risk and the heterogeneous nature of major depressive disorder (MDD). The aim of our study was to determine whether there was a connection between a family history of depression in MDD patients and the presence of putative risk variants in the well-studied SLC6A4, COMT and PCLO genes. We analyzed 133 patients with MDD (30.0% with a positive family history for MDD and 70.0% sporadic cases) and compared them to 279 healthy controls. When comparing all the depressed patients to controls, no significant differences in genotype and allele distributions were detected. After stratifying patients according to their family history, the PCLO rs2522833 C allele was shown to be significantly less common in patients with a positive family history (p = 0.001), indicating a possible difference in the genetic structure of MDD between familial and sporadic cases and a less important role of the common genetic risk variants for the development of MDD in familial cases.

Family history as an important factor for stratifying participants in genetic studies of major depression

University Psychiatric Hospital Ljubljana

Balkan Journal of Medical Genetics

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Depression is estimated to affect 350 million people worldwide. The World Mental Health Survey conducted in 17 countries found that, on average, about one in...

	MDD/GAD Patients (n = 133)	Controls (n = 279)	p Value
PCLO rs2522833
Genotype frequencies:	n (%)	n (%)
AA	59 (0.44)	122 (0.44)
AC	58 (0.43)	112 (0.40)	0.567
CC	16 (0.12)	44 (0.16)
Alleles:
A	176 (0.66)	356 (0.64)	0.549
C	90 (0.34)	176 (0.36)
COMT rs4680
Genotype frequencies:	n (%)	n (%)
GG	26 (0.21)	67 (0.24)
GA	73 (0.56)	154 (0.56)	0.51
AA	31 (0.23)	55 (0.20)
Alleles:
G	125 (0.48)	288 (0.52)
A	135 (0.52)	264 (0.48)	0.276
SLC6A4 50HTTLPR
Genotype frequencies:	n (%)	n (%)
LL	44 (0.34)	100 (0.36)
LS	70 (0.52)	131 (0.48)	0.614
SS	19 (0.14)	45 (0.16)
Alleles:
L	158 (0.59)	331 (0.60)
S	108 (0.41)	221 (0.40)	0.877

	Positive Family History (n = 40)	p Value: Positive Family History vs. Controls	Negative Family History (n = 93)	p Value: Negative Family History vs. Controls	p Value: Positive vs. Negative Family History
PCLO rs2522833
Genotype frequencies:	n (%)		n (%)
AA	26 (0.65)		33 (0.36)
AC	14 (0.35)	0.007	44 (0.47)	0.354	0.001
CC	0 (0.00)		16 (0.17)
Alleles:
A	66 (0.82)		110 (0.59)
C	14 (0.18)	0.001	76 (0.41)	0.232	0.000
COMT rs4680
Genotype frequencies:	n (%)		n (%)
GG	10 (0.25)		16 (0.18)
GA	18 (0.45)	0.297	55 (0.61)	0.439	0.232
AA	12 (0.30)		19 (0.21)
Alleles:
G	38 (0.48)		87 (0.48)
A	42 (0.52)	0.434	93 (0.52)	0.371	0.901
SLC6A4 50HTTLPR
Genotype frequencies:	n (%)		n (%)
LL	18 (0.45)		26 (0.28)
LS	18 (0.45)	0.436	52 (0.56)	0.302	0.148
SS	4 (0.10)		15 (0.16)
Alleles:
L	54 (0.67)		104 (0.56)
S	26 (0.33)	0.197	82 (0.44)	0.332	0.078

Family history as an important factor for stratifying participants in genetic studies of major depression

Article Category: Original Article

Published Online: Oct 29, 2018

Page range: 5 - 12

DOI: https://doi.org/10.2478/bjmg-2018-0010

Keywords
gene, Family history, Major depressive disorder (MDD), gene, gene

© 2018 Zalar B, Blatnik A, Maver A, Klemenc-Ketiš Z, Peterlin B, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Genotype and allele distributions of the PCLO rs2522833, COMT rs4680 and SLC6A4 5-HTTLPR polymorphic variants in major depressive disorder/generalized anxiety disorder patients and controls.

Genotype and allele distribution of the PCLO rs2522833, COMT rs4680 and SLC6A4 5-HTTLPR polymorphic variants in major depressive disorder/generalized anxiety disorder patients with a positive or negative family history for depressive disorders.

Family history as an important factor for stratifying participants in genetic studies of major depression

Article Category: Original Article

Published Online: Oct 29, 2018

Page range: 5 - 12

DOI: https://doi.org/10.2478/bjmg-2018-0010

Keywordsgene, Family history, Major depressive disorder (MDD), gene, gene

© 2018 Zalar B, Blatnik A, Maver A, Klemenc-Ketiš Z, Peterlin B, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Genotype and allele distributions of the PCLO rs2522833, COMT rs4680 and SLC6A4 5-HTTLPR polymorphic variants in major depressive disorder/generalized anxiety disorder patients and controls.

Genotype and allele distribution of the PCLO rs2522833, COMT rs4680 and SLC6A4 5-HTTLPR polymorphic variants in major depressive disorder/generalized anxiety disorder patients with a positive or negative family history for depressive disorders.

Keywords
gene, Family history, Major depressive disorder (MDD), gene, gene