Post on 05-Jan-2016
description
Fenotype-Genotype associaties op exploratief niveau binnen de PREVEND populatie
FANCY PREVEND
LOGO
Mike W. Zuurman, 16–02-2004, MBG
Microalbuminuria (MA):
Appearance of small but abnormal amounts of albumin in the urine. (protein excretion between 30 and 300 mg during a 24 hour period)
Development of microalbuminuria closely linked to long term blood sugar control.
This risk is increased by :
1. duration of diabetes
2. high blood pressure
3. genetic susceptibility
MA is a risk factor for Renal and Cardiovascular disease
Populatie Groningen
85000 individuen
40000 urine monsters
8500 in polikliniek (MA verrijkt)
Prevention of REnal and Vascular ENd-organ Damage
Fenotypische data Genotypische data
ASSOCIATIE STUDIES
140,0 150,0 160,0 170,0 180,0 190,0 200,0
Length (cm)
0
100
200
300
400
500
600
Fre
qu
ency
Mean = 173,033Std. Dev. = 9,4431N = 8.501
Some basic PREVEND population stats
Normal distribution
4291
4301
Male
Female
GenderCount
Some basic PREVEND population stats
40 60
Age HAL (yrs)
0
20
40
60
80
100
120
140
Fre
qu
ency
Mean = 50,41Std. Dev. = 12,94N = 4.291
Gender: Male
40 60
Age HAL (yrs)
0
30
60
90
120
150
Fre
qu
ency
Mean = 48,07Std. Dev. = 12,299N = 4.300
Gender: Female
0,00 1000,00 2000,00 3000,00 4000,00
Albumin loss 48 hrs mg/24hrs)
0
2.000
4.000
6.000
8.000
10.000
Fre
qu
en
cy
Mean = 32,1599Std. Dev. = 143,23369N = 8.574
UAE distribution in PREVEND population
20 30 40 50 60 70 80
Age HAL (yrs)
0,00
500,00
1000,00
1500,00
2000,00
2500,00
3000,00
Alb
um
in lo
ss 4
8 h
rs m
g/2
4hrs
)
Gender: Male
20 30 40 50 60 70 80
Age HAL (yrs)
0,00
1000,00
2000,00
3000,00
4000,00
5000,00
Alb
um
in lo
ss 4
8 h
rs m
g/2
4hrs
)
Gender: Female
Some basic PREVEND population stats
- never use means, use medians
Normalize distribution using natural logarithm (ln)
-5,00 -4,00 -3,00 -2,00 -1,00 0,00 1,00 2,00
lnlnuae
0
500
1.000
1.500
2.000
Fre
qu
en
cy
Mean = 0,8545Std. Dev. = 0,35405N = 8.574
20 30 40 50 60 70 80
Age HAL (yrs)
-6,00
-4,00
-2,00
0,00
2,00
4,00
lnln
uae
Gender: Female
20 30 40 50 60 70 80
Age HAL (yrs)
-6,00
-4,00
-2,00
0,00
2,00
4,00
lnln
uae
Gender: Male
Some basic PREVEND population stats
Coefficientsa,b,c
,460 ,021 22,332 ,000
,009 ,000 ,329 22,765 ,000
(Constant)
Age HAL (yrs)
Model1
B Std. Error
UnstandardizedCoefficients
Beta
StandardizedCoefficients
t Sig.
Dependent Variable: lnlnuaea.
Selecting only cases for which Gender = Maleb.
Gender = Malec.
28 30 32 34 36 3840 42 44 46 48 50 52 54 56 58 60 62 64 66 68 70 72 74
Age HAL (yrs)
0,70
0,80
0,90
1,00
1,10
1,20
Mea
n A
LL
PR
ED
1
Gender
Male
Female
Coefficientsa
,593 ,021 28,316 ,000
,004 ,000 ,151 10,000 ,000
(Constant)
Age HAL (yrs)
Model1
B Std. Error
UnstandardizedCoefficients
Beta
StandardizedCoefficients
t Sig.
Dependent Variable: lnlnuaea.
Some basic PREVEND population stats
Simple linear model lnlnUAE vs Age
28 30 32 34 36 3840 42 44 46 48 50 52 54 56 58 60 62 64 66 68 70 72 74
Age HAL (yrs)
7,50
10,00
12,50
15,00
17,50
20,00
22,50
Mea
n A
LL
PR
ED
1_E
XP
Gender
Male
Female
Dot/Lines show Means
-9,00 21-30 31-40 41-50 51-60 61-70 >70
Age group (steps of 10 years)
0,60
0,80
1,00
lnln
uae
Male Female
-9,00 21-30 31-40 41-50 51-60 61-70 >70
Age group (steps of 10 years)
Some basic PREVEND population stats
Choice of analysis wether Genotypical or Phenotypical
- Investigate those in the younger groups that show MA
- Investigate those in the older area, they aren’t dead so they must be doing something right!
Some basic PREVEND population stats
Choice of confounders and effect modifiers (interactors)
-Age-Gender-Body Mass Index (BMI)-Mean Arterial Bloodpressure (MAP)-Creatinine Clearance / Cockcroft-Gault prediction (CCR)-Urinary Salt Excretion
20,00 40,00 60,00
BMI
0
100
200
300
400
500
600
700
Fre
qu
ency
Mean = 26,1093Std. Dev. = 4,24828N = 8.498
Some basic PREVEND population stats
16,3119,4320,4321,0221,6322,1622,6423,1623,6224,1324,5825,0425,4825,9626,4226,9027,4027,9228,5129,1429,7630,4831,3132,2833,6935,5640,27
BMI
0,60
0,80
1,00
1,20
1,40
1,60
1,80
2,00
Mea
n A
LL
PR
ED
1
Gender
Male
Female
BMI
MAP
80,00 100,00 120,00 140,00
Mean arterial pressure (mmHg)
0
100
200
300
400
500
600
Fre
qu
ency
Mean = 92,3731Std. Dev. = 12,48658N = 8.588 63,33
67,0070,3373,3376,3379,3382,3385,3388,3391,3394,3397,33100,33103,33106,33109,33112,33115,33118,33121,33124,33127,33130,33133,67136,67144,00
Mean arterial pressure (mmHg)
0,40
0,60
0,80
1,00
1,20
1,40
1,60
Mea
n A
LL
PR
ED
1
Gender
Male
Female
63,3367,6771,0074,3377,6781,0084,3387,6791,0094,3397,67101,00104,33107,67111,00114,33117,67121,00124,33127,67131,00134,67139,00149,00
Mean arterial pressure (mmHg)
0,00
25,00
50,00
75,00
100,00
125,00
Mea
n A
LL
PR
ED
1_E
XP
Gender
Male
Female
Angiotensin II
AT1R
vasoconstriction aldosterone excretion
Sodium/potassium concentrations
Fluid retention
Bloodpressure
PART of the Renin-Angiotension-System ™
kidney
ATR1 A/C Polymorphism
246 5,7% 172 4,0%
2031 47,3% 2050 47,7%
1661 38,7% 1704 39,6%
353 8,2% 375 8,7%
AA
AC
CC
AGTRAT1A/C
Count Column %
Male
Count Column %
Female
Gender
AA AC CC
AGTR AT1 A/C
0
20
40
60
80
100
Per
cen
t
Age group (steps of
10 years)
21-30
31-40
41-50
51-60
61-70
>70
Hardy-Weinberg
No significant differences between Age groups
80,00
90,00
100,00
110,00
Mea
n a
rter
ial p
ress
ure
(mm
Hg)
AA
AC CC
30 40 50 60 70
Age HAL (yrs)
80,00
90,00
100,00
110,00
Mea
n a
rter
ial p
ress
ure
(mm
Hg)
30 40 50 60 70
Age HAL (yrs)
Dot/Lines show Means
Some basic PREVEND population stats
MAP versus Age by AT1R genotype
28 30 32 34 36 3840 42 44 46 48 50 52 54 56 5860 62 64 66 68 70 72 74
Age HAL (yrs)
80,00
85,00
90,00
95,00
100,00
105,00
Me
an
AL
LP
RE
D2
_A
T
AGTR AT1 A/C
AA
AC
CC
Some basic PREVEND population stats
MAP versus Age by AT1R genotype
29 31 33 35 37 39
41 43 45 47 49 51 53 55 57 59
Age HAL (yrs)
80
85
90
95
100
Me
an
AL
LP
RE
D2
_A
T
AGTR AT1 A/C
AA
AC
CC
Total population
30 32 34 36 38
40 42 44 46 48 50 52 54 56 58
60
Age HAL (yrs)
80
85
90
95
100
105
110
Me
an
AL
LP
RE
D2
_A
T
AGTR AT1 A/C
AA
AC
CC
Gender: Male
Some basic PREVEND population stats
MAP versus Age by AT1R genotype
Total population
Male
30 32 34 36 38
40 42 44 46 48 50 52 54 56 58
60
Age HAL (yrs)
80
85
90
95
100
105
110
Me
an
AL
LP
RE
D2
_A
T
AGTR AT1 A/C
AA
AC
CC
Gender: Female
Female